Separation of malignant human breast cancer epithelial cells from healthy epithelial cells using an advanced dielectrophoresis-activated cell sorter (DACS).

PubMed

An, Jaemin; Lee, Jangwon; Lee, Sang Ho; Park, Jungyul; Kim, Byungkyu

2009-06-01

In this paper, we successfully separated malignant human breast cancer epithelial cells (MCF 7) from healthy breast cells (MCF 10A) and analyzed the main parameters that influence the separation efficiency with an advanced dielectrophoresis (DEP)-activated cell sorter (DACS). Using the efficient DACS, the malignant cancer cells (MCF 7) were isolated successfully by noninvasive methods from normal cells with similar cell size distributions (MCF 10A), depending on differences between their material properties such as conductivity and permittivity, because our system was able to discern the subtle differences in the properties by generating continuously changed electrical field gradients. In order to evaluate the separation performance without considering size variations, the cells collected from each outlet were divided into size-dependent groups and counted statistically. Following that, the quantitative relative ratio of numbers between MCF 7 and MCF 10A cells in each size-dependent group separated by the DEP were compared according to applied frequencies in the range 48, 51, and 53 MHz with an applied amplitude of 8 V(pp). Finally, under the applied voltage of 48 MHz-8 V(pp) and a flow rate of 290 microm/s, MCF 7 and MCF 10A cells were separated with a maximum efficiency of 86.67% and 98.73% respectively. Therefore, our suggested system shows it can be used for detection and separation of cancerous epithelial cells from noncancerous cells in clinical applications.

Distinct pattern separation related transfer functions in human CA3/dentate and CA1 revealed using high-resolution fMRI and variable mnemonic similarity

PubMed Central

Lacy, Joyce W.; Yassa, Michael A.; Stark, Shauna M.; Muftuler, L. Tugan; Stark, Craig E.L.

2011-01-01

Producing and maintaining distinct (orthogonal) neural representations for similar events is critical to avoiding interference in long-term memory. Recently, our laboratory provided the first evidence for separation-like signals in the human CA3/dentate. Here, we extended this by parametrically varying the change in input (similarity) while monitoring CA1 and CA3/dentate for separation and completion-like signals using high-resolution fMRI. In the CA1, activity varied in a graded fashion in response to increases in the change in input. In contrast, the CA3/dentate showed a stepwise transfer function that was highly sensitive to small changes in input. PMID:21164173

Business Education Resources.

ERIC Educational Resources Information Center

Alaska State Dept. of Education, Juneau. Div. of Adult and Vocational Education.

This guide contains instructional materials to aid business education teachers in teaching business skills in Alaska secondary schools. The materials include five units covering the following topics: human relations as a separate unit and as integrated into other daily activities such as planning and organizing work activities and grooming,…

Why are maternally separated females inflexible? Brain activity pattern of COx and c-Fos.

PubMed

Banqueri, María; Méndez, Marta; Arias, Jorge L

2018-06-15

Subjects' early life events will affect them later in life. When these events are stressful, such as child abuse in humans or repeated maternal separation in rodents, subjects can show some behavioral and brain alterations. This study used young adult female Wistar rats that were maternally raised (AFR), maternally separated from post-natal day (PND) 1 to PND10 (MS10), or maternally separated from PND1 to PND21 (MS21), in order to assess the effects of maternal separation (MS) on spatial learning and memory, as well as cognitive flexibility, using the Morris Water Maze (MWM). We performed quantitative cytochrome oxidase (COx) histochemistry on selected brain areas in order to identify whether maternal separation affects brain energy metabolism. We also performed c-Fos immunohistochemistry on the medial prefrontal cortex (mPFC), thalamus, and hippocampus to explore whether this immediate early gene activity was altered in stressed subjects. We obtained a similar spatial learning pattern in maternally raised and maternally separated subjects on the reference memory task, but only the controls were flexible enough to solve the reversal learning successfully. Separated groups showed less c-Fos activity in the mPFC and less complex neural networks on COx. Copyright © 2018 Elsevier Inc. All rights reserved.

Cytotoxic activity of Cuphea aequipetala.

PubMed

Avila, Elisa Vega; Aguilar, Rafaela Tapia; Estrada, Manuel Jiménez; Ortega, Ma Luisa Villarreal; Ramos, Rubén Román

2004-01-01

Cuphea aequipetala (Lytraceae) is a perennial plant that has been used in Mexican traditional medicine to treat different types of tumors since prehispanic times. In the present work the cytotoxic potential of different fractions from acetone-water extract from the whole plant was investigated using a sulforhodamine B assay. Fractions were subjected to a bioscreening assay using several cell lines: HEp-2 (human larynx carcinoma), HCT-15 (human colon cancer) and DU-145 (human prostate carcinoma). Colchicine was used as positive control. Data are presented as the dose that inhibited 50.0% control growth (ED50). The cytotoxic activity is selective since the ED50 is different for the three cell lines employed. The highest activity was seen against the DU-145 cell line. "E" and PB1 fractions had the highest cytotoxic activities with ED50 values of 0.418 and 2.40 microg/ml respectively, on the DU-145 cell line. The "E" fraction was a yellow powder; it was methanol soluble and contained at least four separate components when separated by thin-layer chromatography. PB1 was a solid with metallic appearance; it was water soluble and its two dimensional chromatography showed 9 spots. These fractions have cytotoxic actives because their ED50 is less than 20 microg/ml and they will be further characterized.

Amidase Activity of AmiC Controls Cell Separation and Stem Peptide Release and Is Enhanced by NlpD in Neisseria gonorrhoeae.

PubMed

Lenz, Jonathan D; Stohl, Elizabeth A; Robertson, Rosanna M; Hackett, Kathleen T; Fisher, Kathryn; Xiong, Kalia; Lee, Mijoon; Hesek, Dusan; Mobashery, Shahriar; Seifert, H Steven; Davies, Christopher; Dillard, Joseph P

2016-05-13

The human-restricted pathogen Neisseria gonorrhoeae encodes a single N-acetylmuramyl-l-alanine amidase involved in cell separation (AmiC), as compared with three largely redundant cell separation amidases found in Escherichia coli (AmiA, AmiB, and AmiC). Deletion of amiC from N. gonorrhoeae results in severely impaired cell separation and altered peptidoglycan (PG) fragment release, but little else is known about how AmiC functions in gonococci. Here, we demonstrated that gonococcal AmiC can act on macromolecular PG to liberate cross-linked and non-cross-linked peptides indicative of amidase activity, and we provided the first evidence that a cell separation amidase can utilize a small synthetic PG fragment as substrate (GlcNAc-MurNAc(pentapeptide)-GlcNAc-MurNAc(pentapeptide)). An investigation of two residues in the active site of AmiC revealed that Glu-229 is critical for both normal cell separation and the release of PG fragments by gonococci during growth. In contrast, Gln-316 has an autoinhibitory role, and its mutation to lysine resulted in an AmiC with increased enzymatic activity on macromolecular PG and on the synthetic PG derivative. Curiously, the same Q316K mutation that increased AmiC activity also resulted in cell separation and PG fragment release defects, indicating that activation state is not the only factor determining normal AmiC activity. In addition to displaying high basal activity on PG, gonococcal AmiC can utilize metal ions other than the zinc cofactor typically used by cell separation amidases, potentially protecting its ability to function in zinc-limiting environments. Thus gonococcal AmiC has distinct differences from related enzymes, and these studies revealed parameters for how AmiC functions in cell separation and PG fragment release. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

76 FR 35897 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-20

... nonambulatory disabled cattle, and mechanically separated (MS)(Beef). Under the regulations, no human food or... must send a written request to the Director, Center for Food Safety and Applied Nutrition (CFSAN). The... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0264...

Urokinase production by electrophoretically separated cultured human embryonic kidney cells

NASA Technical Reports Server (NTRS)

Kunze, M. E.; Plank, L. D.; Giranda, V.; Sedor, K.; Todd, P. W.

1985-01-01

Urokinase is a plasminogen activator found in urine. Relatively pure preparations have been tested in Europe, Japan and the United States for the treatment of deep vein thrombosis and other dangerous blood clots. Human embryonic kidney cell cultures have been found to produce urokinase at much higher concentrations, but less than 5% of the cells in typical cultures are producers. Since human diploid cells become senescent in culture the selection of clones derived from single cells will not provide enough material to be useful, so a bulk purification method is needed for the isolation of urokinase producing cell populations. Preparative cell electrophoresis was chosen as the method, since evidence exists that human embryonic cell cultures are richly heterogeneous with respect to electrophoretic mobility, and preliminary electrophoretic separations on the Apollo-Soyuz space flight produced cell populations that were rich in urokinase production. Similarly, erythropoietin is useful in the treatment of certain anemias and is a kidney cell duct, and electrophoretically enriched cell populations producing this product have been reported. Thus, there is a clear need for diploid human cells that produce these products, and there is evidence that such cells should be separable by free-flow cell electrophoresis.

M-X Environmental Technical Report. Alternative Potential Operating Base Locations: Ely.

DTIC Science & Technology

1980-12-22

and Vicinity Community Environment 1 1.1 Human Environment 1.1.1 Economic Activity 1.1.2 Public Finance 3 1.1.3 Population A8 1.1.4 Land Use 16 1.1.5...Base Vicinity 63 2.1 Human Environment 63 2.1.1 Effects on Employment (Jobs) and Labor Force 63 2.1.2 Effects on Income and Earnings 66 2.1.3 Effects...vicinity. 1.1 HUMAN ENVIRONMENT Economic Activity (1.1.1) Once a part of Lander County, White Pine County was organized separately on April 1, 1869. This was

Functional Allocation with Airborne Self-Separation Evaluated in a Piloted Simulation

NASA Technical Reports Server (NTRS)

Wing, David J.; Murdoch, Jennifer L.; Chamberlain, James P.; Consiglio, Maria C.; Hoardley, Sherwood T.; Hubbs, Clay E.; Palmer, Michael T.

2010-01-01

A human-in-the-loop simulation experiment was designed and conducted to evaluate an airborne self-separation concept. The activity supports the National Aeronautics and Space Administration s (NASA) research focus on function allocation for separation assurance. The objectives of the experiment were twofold: (1) use experiment design features in common with a companion study of ground-based automated separation assurance to promote comparability, and (2) assess agility of self-separation operations in managing trajectory-changing events in high traffic density, en-route operations with arrival time constraints. This paper describes the experiment and presents initial results associated with subjective workload ratings and group discussion feedback obtained from the experiment s commercial transport pilot participants.

ATM directs DNA damage responses and proteostasis via genetically separable pathways

PubMed Central

Lee, Ji-Hoon; Mand, Michael R.; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W.; Richards, Alicia L.; Coon, Joshua J.; Paull, Tanya T.

2018-01-01

The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes Ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. Here, we genetically separated DNA damage activation of ATM from oxidative activation using separation-of-function mutations. We found that deficiency in ATM activation by Mre11-Rad50-Nbs1 and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of ATM lacking oxidative activation generates widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicates ATM in the control of protein homeostasis. PMID:29317520

Decoding Spontaneous Emotional States in the Human Brain

PubMed Central

Kragel, Philip A.; Knodt, Annchen R.; Hariri, Ahmad R.; LaBar, Kevin S.

2016-01-01

Pattern classification of human brain activity provides unique insight into the neural underpinnings of diverse mental states. These multivariate tools have recently been used within the field of affective neuroscience to classify distributed patterns of brain activation evoked during emotion induction procedures. Here we assess whether neural models developed to discriminate among distinct emotion categories exhibit predictive validity in the absence of exteroceptive emotional stimulation. In two experiments, we show that spontaneous fluctuations in human resting-state brain activity can be decoded into categories of experience delineating unique emotional states that exhibit spatiotemporal coherence, covary with individual differences in mood and personality traits, and predict on-line, self-reported feelings. These findings validate objective, brain-based models of emotion and show how emotional states dynamically emerge from the activity of separable neural systems. PMID:27627738

Demonstration of separate phosphotyrosyl- and phosphoseryl- histone phosphatase activities in the plasma membranes of a human astrocytoma.

PubMed

Leis, J F; Knowles, A F; Kaplan, N O

1985-06-01

A plasma membrane preparation from a human astrocytoma contained p-nitrophenyl phosphate (pNPP), phosphotyrosyl histone, and phosphoseryl histone hydrolysis activities. The pNPPase and phosphotyrosyl histone phosphatase activities were inhibited by vanadate, whereas the phosphoseryl histone phosphatase activity was not; the latter activity was inhibited by pyrophosphate and nucleoside di- and triphosphates. When the membranes were solubilized by Triton X-100 and the solubilized proteins were subjected to column chromatography on DEAE-Sephadex, Sepharose 6B-C1, and wheat germ agglutinin-Sepharose 4B columns, the pNPPase activity from the phosphoseryl histone phosphatase activity. The results from column chromatography also indicated that there may be multiple phosphotyrosyl and phosphoseryl protein phosphatases in the plasma membranes.

Separation of lymphocytes by electrophoresis under terrestrial conditions and at zero gravity

NASA Technical Reports Server (NTRS)

Rubin, A. L.

1977-01-01

Electrophoretic mobility (EPM) of human peripheral lymphocytes were examined with the following objectives: To determine differences in EPM of lymphocytes under immuno-stimulated and immuno-suppressed states. To define the conditions necessary for the separation of lymphocyte sub-populations in normal and pathological conditions; To investigate immunological active, charged chemical groups on lymphocyte surfaces; and to investigate pathophysiological mechanisms of immune responsiveness, as reflected by alterations in EPM. To evaluate the potential of lymphocyte electrophoresis as: (1) a means of monitoring the immune status of kidney transplant recipients, (2) in predicting the outcome of kidney transplants, and (3) as a method for separation of lymphocyte sub-populations, the EPM was studied for unfractionated human peripheral lymphocytes and of populations enriched with T and "B" cells from normal adults, hemodialysis patients and kidney transplant recipients.

Assessment of human natural killer and lymphokine-activated killer cell cytotoxicity against Toxoplasma gondii trophozoites and brain cysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dannemann, B.R.; Morris, V.A.; Araujo, F.G.

1989-10-15

Because previous work has suggested that NK cells may be important in host resistance against the intracellular parasite Toxoplasma gondii we examined whether human NK cells and lymphokine-activated killer (LAK) cells have activity against trophozoites and cysts of this organism in vitro. A method to radiolabel Toxoplasma trophozoites with 51Cr was developed and direct cytotoxic activity was determined by using modifications of the standard 51Cr release assay. Viability of 51Cr-labeled trophozoites assessed by both methylene blue staining and trypan blue exclusion was greater than 90%. Significantly more 51Cr was released by anti-Toxoplasma antibody and C than by antibody in themore » absence of C. Incubation of trophozoites with freshly isolated human NK cells or NK cells activated with either rIL-2 or rIFN-alpha did not result in significant release of 51Cr (specific lysis was 0 to 2.3%). In contrast, the average specific lysis of radiolabeled trophozoites by LAK cells was significant. In a series of separate experiments, preincubation of radiolabeled trophozoites with heat-inactivated normal or Toxoplasma antibody-positive human serum increased the cytotoxicity of LAK cells from a mean specific lysis of 15% +/- 4.5 to 39% +/- 8.5, respectively, as assessed by 51Cr release. Because previous work has shown that radioisotope release from parasites may be nonspecific, separate experiments were performed to determine the cytotoxicity of LAK cells against antibody-coated trophozoites by using ethidium bromide-acridine orange staining to assess effector cell damage. LAK cells had a mean specific lysis of 51% against antibody-coated trophozoites by ethidium bromide-acridine orange staining. Preincubation with heat-inactivated Toxoplasma-antibody positive human serum did not increase activity of rIL-2-activated NK cells against 51CR-labeled trophozoites.« less

Carbon Dioxide Separation from Flue Gases: A Technological Review Emphasizing Reduction in Greenhouse Gas Emissions

PubMed Central

Songolzadeh, Mohammad; Soleimani, Mansooreh; Takht Ravanchi, Maryam; Songolzadeh, Reza

2014-01-01

Increasing concentrations of greenhouse gases (GHGs) such as CO2 in the atmosphere is a global warming. Human activities are a major cause of increased CO2 concentration in atmosphere, as in recent decade, two-third of greenhouse effect was caused by human activities. Carbon capture and storage (CCS) is a major strategy that can be used to reduce GHGs emission. There are three methods for CCS: pre-combustion capture, oxy-fuel process, and post-combustion capture. Among them, post-combustion capture is the most important one because it offers flexibility and it can be easily added to the operational units. Various technologies are used for CO2 capture, some of them include: absorption, adsorption, cryogenic distillation, and membrane separation. In this paper, various technologies for post-combustion are compared and the best condition for using each technology is identified. PMID:24696663

High-performance liquid chromatographic determination of loxoprofen and its diastereomeric alcohol metabolites in biological fluids by fluorescence labelling with 4-bromomethyl-6,7-methylenedioxycoumarin.

PubMed

Naganuma, H; Kawahara, Y

1990-09-14

A simple and sensitive high-performance liquid chromatographic procedure to determine loxoprofen and its diastereomeric alcohol metabolites in biological specimens is described. The analysis involves liquid-liquid extraction with benzene, pre-column derivatization with a highly fluorogenic reagent, 4-bromomethyl-6,7-methylenedioxycoumarin (BrMDC) and subsequent separation on a reversed-phase column. Loxoprofen, its pharmacologically active metabolite, trans-alcohol, and less active cis-alcohol were completely separated within 20 min with a mobile phase of 55% of aqueous acetonitrile containing acetic acid. Any endogenous substances do not interfere in the analysis of either plasma or urine samples. The quantitation limit was 0.01 micrograms/ml for human plasma and 0.05 micrograms/ml for urine. The method was applied to a pharmacokinetic study in healthy human subjects who had received 60 mg of loxoprofen sodium.

Carbon dioxide separation from flue gases: a technological review emphasizing reduction in greenhouse gas emissions.

PubMed

Songolzadeh, Mohammad; Soleimani, Mansooreh; Takht Ravanchi, Maryam; Songolzadeh, Reza

2014-01-01

Increasing concentrations of greenhouse gases (GHGs) such as CO2 in the atmosphere is a global warming. Human activities are a major cause of increased CO2 concentration in atmosphere, as in recent decade, two-third of greenhouse effect was caused by human activities. Carbon capture and storage (CCS) is a major strategy that can be used to reduce GHGs emission. There are three methods for CCS: pre-combustion capture, oxy-fuel process, and post-combustion capture. Among them, post-combustion capture is the most important one because it offers flexibility and it can be easily added to the operational units. Various technologies are used for CO2 capture, some of them include: absorption, adsorption, cryogenic distillation, and membrane separation. In this paper, various technologies for post-combustion are compared and the best condition for using each technology is identified.

Separating Movement and Gravity Components in an Acceleration Signal and Implications for the Assessment of Human Daily Physical Activity

PubMed Central

van Hees, Vincent T.; Gorzelniak, Lukas; Dean León, Emmanuel Carlos; Eder, Martin; Pias, Marcelo; Taherian, Salman; Ekelund, Ulf; Renström, Frida; Franks, Paul W.; Horsch, Alexander; Brage, Søren

2013-01-01

Introduction Human body acceleration is often used as an indicator of daily physical activity in epidemiological research. Raw acceleration signals contain three basic components: movement, gravity, and noise. Separation of these becomes increasingly difficult during rotational movements. We aimed to evaluate five different methods (metrics) of processing acceleration signals on their ability to remove the gravitational component of acceleration during standardised mechanical movements and the implications for human daily physical activity assessment. Methods An industrial robot rotated accelerometers in the vertical plane. Radius, frequency, and angular range of motion were systematically varied. Three metrics (Euclidian norm minus one [ENMO], Euclidian norm of the high-pass filtered signals [HFEN], and HFEN plus Euclidean norm of low-pass filtered signals minus 1 g [HFEN+]) were derived for each experimental condition and compared against the reference acceleration (forward kinematics) of the robot arm. We then compared metrics derived from human acceleration signals from the wrist and hip in 97 adults (22–65 yr), and wrist in 63 women (20–35 yr) in whom daily activity-related energy expenditure (PAEE) was available. Results In the robot experiment, HFEN+ had lowest error during (vertical plane) rotations at an oscillating frequency higher than the filter cut-off frequency while for lower frequencies ENMO performed better. In the human experiments, metrics HFEN and ENMO on hip were most discrepant (within- and between-individual explained variance of 0.90 and 0.46, respectively). ENMO, HFEN and HFEN+ explained 34%, 30% and 36% of the variance in daily PAEE, respectively, compared to 26% for a metric which did not attempt to remove the gravitational component (metric EN). Conclusion In conclusion, none of the metrics as evaluated systematically outperformed all other metrics across a wide range of standardised kinematic conditions. However, choice of metric explains different degrees of variance in daily human physical activity. PMID:23626718

Separating movement and gravity components in an acceleration signal and implications for the assessment of human daily physical activity.

PubMed

van Hees, Vincent T; Gorzelniak, Lukas; Dean León, Emmanuel Carlos; Eder, Martin; Pias, Marcelo; Taherian, Salman; Ekelund, Ulf; Renström, Frida; Franks, Paul W; Horsch, Alexander; Brage, Søren

2013-01-01

Human body acceleration is often used as an indicator of daily physical activity in epidemiological research. Raw acceleration signals contain three basic components: movement, gravity, and noise. Separation of these becomes increasingly difficult during rotational movements. We aimed to evaluate five different methods (metrics) of processing acceleration signals on their ability to remove the gravitational component of acceleration during standardised mechanical movements and the implications for human daily physical activity assessment. An industrial robot rotated accelerometers in the vertical plane. Radius, frequency, and angular range of motion were systematically varied. Three metrics (Euclidian norm minus one [ENMO], Euclidian norm of the high-pass filtered signals [HFEN], and HFEN plus Euclidean norm of low-pass filtered signals minus 1 g [HFEN+]) were derived for each experimental condition and compared against the reference acceleration (forward kinematics) of the robot arm. We then compared metrics derived from human acceleration signals from the wrist and hip in 97 adults (22-65 yr), and wrist in 63 women (20-35 yr) in whom daily activity-related energy expenditure (PAEE) was available. In the robot experiment, HFEN+ had lowest error during (vertical plane) rotations at an oscillating frequency higher than the filter cut-off frequency while for lower frequencies ENMO performed better. In the human experiments, metrics HFEN and ENMO on hip were most discrepant (within- and between-individual explained variance of 0.90 and 0.46, respectively). ENMO, HFEN and HFEN+ explained 34%, 30% and 36% of the variance in daily PAEE, respectively, compared to 26% for a metric which did not attempt to remove the gravitational component (metric EN). In conclusion, none of the metrics as evaluated systematically outperformed all other metrics across a wide range of standardised kinematic conditions. However, choice of metric explains different degrees of variance in daily human physical activity.

Water Walls for Life Support

NASA Technical Reports Server (NTRS)

Hammoudeh, Mona (Inventor); Flynn, Michael T. (Inventor); Gormly, Sherwin J. (Inventor); Richardson, Tra-My Justine (Inventor)

2017-01-01

A method and associated system for processing waste gases, liquids and solids, produced by human activity, to separate (i) liquids suitable for processing to produce potable water, (ii) solids and liquids suitable for construction of walls suitable for enclosing a habitat volume and for radiation shielding, and (iii) other fluids and solids that are not suitable for processing. A forward osmosis process and a reverse osmosis process are sequentially combined to reduce fouling and to permit accumulation of different processable substances. The invention may be used for long term life support of human activity.

Peptide inhibitor modified magnetic particles for pepsin separation.

PubMed

Filuszová, Michaela; Kucerová, Zdenka; Tichá, Marie

2009-06-01

Synthetic heptapeptide containing D-amino acid residues (Val-D-Leu-Pro-Phe-Phe-Val-D-Leu) was coupled to glyoxal-activated magnetic agarose particles via the free peptide amino group. The peptide-modified magnetic particles were used for the separation of pepsins. Porcine pepsin A and human pepsin A were adsorbed to the magnetic peptide-modified affinity carrier, while the rat pepsin C and human pepsin C did not interact with the immobilized ligand. Conditions of pepsin adsorption to peptide-modified magnetic particles, as well as elution buffers were optimized. Porcine pepsin A did not interact with the immobilized peptide in the presence of pepsin inhibitor pepstatin A, indicating that the enzyme binding site is involved in the studied interaction. The elaborated method represents a rapid and simple technique not only for the separation of pepsins but also, in combination with MS, for the enzyme detection and determination.

Purification and cultivation of human pituitary growth hormone secreting cells

NASA Technical Reports Server (NTRS)

Hymer, W. C.

1979-01-01

Efforts were directed towards maintenance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro. The production of human growth hormone (hGH) by this means would be of benefit for the treatment of certain human hypopituitary diseases such as dwarfism. One of the primary approaches was the testing of agents which may logically be expected to increase hGH release. The progress towards this goal is summarized. Results from preliminary experiments dealing with electrophoresis of pituitary cell for the purpose of somatotroph separation are described.

Energy efficient reconcentration of diluted human urine using ion exchange membranes in bioelectrochemical systems.

PubMed

Tice, Ryan C; Kim, Younggy

2014-11-01

Nutrients can be recovered from source separated human urine; however, nutrient reconcentration (i.e., volume reduction of collected urine) requires energy-intensive treatment processes, making it practically difficult to utilize human urine. In this study, energy-efficient nutrient reconcentration was demonstrated using ion exchange membranes (IEMs) in a microbial electrolysis cell (MEC) where substrate oxidation at the MEC anode provides energy for the separation of nutrient ions (e.g., NH4(+), HPO4(2-)). The rate of nutrient separation was magnified with increasing number of IEM pairs and electric voltage application (Eap). Ammonia and phosphate were reconcentrated from diluted human urine by a factor of up to 4.5 and 3.0, respectively (Eap = 1.2 V; 3-IEM pairs). The concentrating factor increased with increasing degrees of volume reduction, but it remained stationary when the volume ratio between the diluate (urine solution that is diluted in the IEM stack) and concentrate (urine solution that is reconcentrated) was 6 or greater. The energy requirement normalized by the mass of nutrient reconcentrated was 6.48 MJ/kg-N (1.80 kWh/kg-N) and 117.6 MJ/kg-P (32.7 kWh/kg-P). In addition to nutrient separation, the examined MEC reactor with three IEM pairs showed 54% removal of COD (chemical oxygen demand) in 47-hr batch operation. The high sulfate concentration in human urine resulted in substantial growth of both of acetate-oxidizing and H2-oxidizing sulfate reducing bacteria, greatly diminishing the energy recovery and Coulombic efficiency. However, the high microbial activity of sulfate reducing bacteria hardly affected the rate of nutrient reconcentration. With the capability to reconcentrate nutrients at a minimal energy consumption and simultaneous COD removal, the examined bioelectrochemical treatment method with an IEM application has a potential for practical nutrient recovery and sustainable treatment of source-separated human urine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Persistent neural activity in auditory cortex is related to auditory working memory in humans and nonhuman primates

PubMed Central

Huang, Ying; Matysiak, Artur; Heil, Peter; König, Reinhard; Brosch, Michael

2016-01-01

Working memory is the cognitive capacity of short-term storage of information for goal-directed behaviors. Where and how this capacity is implemented in the brain are unresolved questions. We show that auditory cortex stores information by persistent changes of neural activity. We separated activity related to working memory from activity related to other mental processes by having humans and monkeys perform different tasks with varying working memory demands on the same sound sequences. Working memory was reflected in the spiking activity of individual neurons in auditory cortex and in the activity of neuronal populations, that is, in local field potentials and magnetic fields. Our results provide direct support for the idea that temporary storage of information recruits the same brain areas that also process the information. Because similar activity was observed in the two species, the cellular bases of some auditory working memory processes in humans can be studied in monkeys. DOI: http://dx.doi.org/10.7554/eLife.15441.001 PMID:27438411

Biodegradation of composite resin with ester linkages: identifying human salivary enzyme activity with a potential role in the esterolytic process.

PubMed

Cai, Kuihua; Delaviz, Yasaman; Banh, Michael; Guo, Yi; Santerre, J Paul

2014-08-01

The ester linkages contained within dental resin monomers (such as Bisphenol A-glycidylmethacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA)) are susceptible to hydrolytic degradation by salivary esterases, however very little is known about the specific esterase activities implicated in this process. The objective of this work was to isolate and identify the dominant proteins from saliva that are associated with the esterase activities shown to be involved in the degradation of BisGMA. Human whole saliva was collected and processed prior to separation in a HiPrep 16/60 Sephacryl S-200 HR column. The fraction with the highest esterase activity was further separated by an anion exchange column (Mono-Q (10/100G)). Isolated fractions were then separated by gel electrophoresis, and compared to a common bench marker esterase, cholesterol esterase (CE), and commercial albumin which has been reported to express esterase activity. Proteins suspected of containing esterase activity were analyzed by Mass Spectroscopy (MS). Commercially available proteins, similar to the salivary esterase proteins identified by MS, were used to replicate the enzymatic complexes and confirm their degradation activity with respect to BisGMA. MS data suggested that the enzyme fraction with the highest esterase activity was contained among a group of proteins consisting of albumin, Zn-α2-glycoprotein, α-amylase, TALDO1 protein, transferrin, lipocalin2, and prolactin-induced protein. Studies concluded that the main esterase bands on the gels in each fraction did not overlap with CE activity, and that albumin activity emerged as a lead candidate with significant esterase activity relative to BisGMA degradation, particularly when it formed a complex with Zn-α2-glycoprotein, under slightly basic conditions. These enzyme complexes can be used as a physiologically relevant formulation to test the biostability of composite resins. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Simultaneous screening of four epidermal growth factor receptor antagonists from Curcuma longa via cell membrane chromatography online coupled with HPLC-MS.

PubMed

Sun, Meng; Ma, Wei-na; Guo, Ying; Hu, Zhi-gang; He, Lang-chong

2013-07-01

The epidermal growth factor receptors (EGFRs) are significant targets for screening active compounds. In this work, an analytical method was established for rapid screening, separation, and identification of EGFRs antagonists from Curcuma longa. Human embryonic kidney 293 cells with a steadily high expression of EGFRs were used to prepare the cell membrane stationary phase in a cell membrane chromatography model for screening active compounds. Separation and identification of the retention chromatographic peaks was achieved by HPLC-MS. The active sites, docking extents and inhibitory effects of the active compounds were also demonstrated. The screening result found that ar-turmerone, curcumin, demethoxycurcumin, and bisdemethoxycurcumin from Curcuma longa could be active components in a similar manner to gefitinib. Biological trials showed that all of four compounds can inhibit EGFRs protein secretion and cell growth in a dose-dependent manner, and downregulate the phosphorylation of EGFRs. This analytical method demonstrated fast and effective characteristics for screening, separation and identification of the active compounds from a complex system and should be useful for drug discovery with natural medicinal herbs. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hydrogen peroxide yields mechanistic insights into human mRNA capping enzyme function

PubMed Central

Mullen, Nicholas J.

2017-01-01

Capping of nascent RNA polymerase II (Pol II) transcripts is required for gene expression and the first two steps are catalyzed by separate 5′ triphosphatase and guanylyltransferase activities of the human capping enzyme (HCE). The cap is added co-transcriptionally, but how the two activities are coordinated is unclear. Our previous in vitro work has suggested that an unidentified factor modulates the minimum length at which nascent transcripts can be capped. Using the same well-established in vitro system with hydrogen peroxide as a capping inhibitor, we show that this unidentified factor targets the guanylyltransferase activity of HCE. We also uncover the mechanism of HCE inhibition by hydrogen peroxide, and by using mass spectrometry demonstrate that the active site cysteine residue of the HCE triphosphatase domain becomes oxidized. Using recombinant proteins for the two separated HCE domains, we provide evidence that the triphosphatase normally acts on transcripts shorter than can be acted upon by the guanylyltransferase. Our further characterization of the capping reaction dependence on transcript length and its interaction with the unidentified modulator of capping raises the interesting possibility that the capping reaction could be regulated. PMID:29028835

Scale-Free Fluctuations in Behavioral Performance: Delineating Changes in Spontaneous Behavior of Humans with Induced Sleep Deficiency

PubMed Central

Beldzik, Ewa; Chialvo, Dante R.; Domagalik, Aleksandra; Fafrowicz, Magdalena; Gudowska-Nowak, Ewa; Marek, Tadeusz; Nowak, Maciej A.; Oginska, Halszka; Szwed, Jerzy

2014-01-01

The timing and dynamics of many diverse behaviors of mammals, e.g., patterns of animal foraging or human communication in social networks exhibit complex self-similar properties reproducible over multiple time scales. In this paper, we analyze spontaneous locomotor activity of healthy individuals recorded in two different conditions: during a week of regular sleep and a week of chronic partial sleep deprivation. After separating activity from rest with a pre-defined activity threshold, we have detected distinct statistical features of duration times of these two states. The cumulative distributions of activity periods follow a stretched exponential shape, and remain similar for both control and sleep deprived individuals. In contrast, rest periods, which follow power-law statistics over two orders of magnitude, have significantly distinct distributions for these two groups and the difference emerges already after the first night of shortened sleep. We have found steeper distributions for sleep deprived individuals, which indicates fewer long rest periods and more turbulent behavior. This separation of power-law exponents is the main result of our investigations, and might constitute an objective measure demonstrating the severity of sleep deprivation and the effects of sleep disorders. PMID:25222128

Domain of the Gods: Do traditional beliefs hinder public acceptance of the human role in climate change?

NASA Astrophysics Data System (ADS)

Donner, S.

2008-12-01

Public acceptance of new scientific discoveries like natural selection, plate tectonics, or the human role in climate change naturally lags behind the pace of the discoveries. In the case of climate change, unease or outright rejection of the scientific evidence for the role of human activity in climate change has been a hindrance to mitigation and adaptation efforts. This skepticism is normally attributed to everything from the quality of science education, to disinformation campaigns by representatives of the coal and gas industry, to individual resistance to behavioral change, to the nature of the modern information culture. This skepticism of scientific evidence for climate change, though often inspired by politics, economics and the particular dynamics of climate change, may actually be rooted in ancient beliefs that the climate is beyond the influence of humans. In this presentation, I will outline how the notion that humans control or influence the weather runs contrary to thousands of years of belief in a separation between the earth - the domain of man - and sky - the domain of the gods. Evidence from religious history, traditional villages in the Pacific (Fjij and Kiribati) and from public discourse in North America all indicates that the millennia-old belief in an earth-sky separation hinders people's acceptance that human activity is affecting the climate. The human role in climate change therefore represents a substantial paradigm shift, similar to the role of natural selection in human evolution. These deep roots of climate change skepticism must be factored into public climate change education efforts.

Solubilization of adenylyl cyclase from human myometrium in a alphas-coupled form.

PubMed

Bajo, Ana M; Prieto, Juan C; Valenzuela, Pedro; Martinez, Pilar; Guijarro, Luis G

2003-08-01

Adenylyl cyclase (AC) was extracted from human myometrium with either non-ionic (Lubrol-PX or Triton X-100) or zwitterionic (3-[3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, CHAPS) detergents. The soluble enzyme was stimulated by forskolin, a hydrophobic activator, in the presence of Mg2+ indicating that the catalytic subunit had not been damaged after solubilization. The enzyme was also activated by 5'-guanylyl imidodiphosphate (Gpp(NH)p) showing that the catalytic unit was not separated from stimulatory guanine nucleotide binding protein (Gs) during the extraction. Both activators showed different effects on the stimulatory efficacy and potency of AC activity solobulized with detergents. Gel filtration of Lubrol-PX and CHAPS extracts over a Sepharose CL-2B column partially resolved AC and its complexes. The chromatographic profile for Lubrol-solubilized AC presented a main peak of about 200 kDa whereas CHAPS-solubilized AC showed a dominant peak of about 1100 kDa. The heterodisperse peaks obtained revealed that the catalytic AC subunit was not separated from Gs proteins after gel filtration, and that AC could be associated with other cellular proteins. When Lubrol extract was submitted to anionic-exchange chromatography, the enzyme was purified about 7.5 fold (enzymatic activity of 48.1 pmol/min/mg of protein). The catalytic subunit was co-eluted with both AC-activating proteins Galphas large (52.2 kDa) and Galphas small (48.7 kDa). This is the first demonstration of the stable physical association of AC with both alphas subunits of G proteins in human myometrium.

Dopamine D2-receptor blockade enhances decoding of prefrontal signals in humans.

PubMed

Kahnt, Thorsten; Weber, Susanna C; Haker, Helene; Robbins, Trevor W; Tobler, Philippe N

2015-03-04

The prefrontal cortex houses representations critical for ongoing and future behavior expressed in the form of patterns of neural activity. Dopamine has long been suggested to play a key role in the integrity of such representations, with D2-receptor activation rendering them flexible but weak. However, it is currently unknown whether and how D2-receptor activation affects prefrontal representations in humans. In the current study, we use dopamine receptor-specific pharmacology and multivoxel pattern-based functional magnetic resonance imaging to test the hypothesis that blocking D2-receptor activation enhances prefrontal representations. Human subjects performed a simple reward prediction task after double-blind and placebo controlled administration of the D2-receptor antagonist amisulpride. Using a whole-brain searchlight decoding approach we show that D2-receptor blockade enhances decoding of reward signals in the medial orbitofrontal cortex. Examination of activity patterns suggests that amisulpride increases the separation of activity patterns related to reward versus no reward. Moreover, consistent with the cortical distribution of D2 receptors, post hoc analyses showed enhanced decoding of motor signals in motor cortex, but not of visual signals in visual cortex. These results suggest that D2-receptor blockade enhances content-specific representations in frontal cortex, presumably by a dopamine-mediated increase in pattern separation. These findings are in line with a dual-state model of prefrontal dopamine, and provide new insights into the potential mechanism of action of dopaminergic drugs. Copyright © 2015 the authors 0270-6474/15/354104-08$15.00/0.

Na[superscript +] binding to meizothrombin desF1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Papaconstantinou, M.E.; Gandhi, P.S.; Chen, Z.

2009-06-10

Meizothrombin is the physiologically active intermediate generated by a single cleavage of prothrombin at R320 to separate the A and B chains. Recent evidence has suggested that meizothrombin, like thrombin, is a Na{sup +}-activated enzyme. In this study we present the first X-ray crystal structure of human meizothrombin desF1 solved in the presence of the active site inhibitor PPACK at 2.1 {angstrom} resolution. The structure reveals a Na{sup +} binding site whose architecture is practically identical to that of human thrombin. Stopped-flow measurements of Na{sup +} binding to meizothrombin desF1 document a slow phase of fluorescence change with a kmore » obs decreasing hyperbolically with increasing [Na{sup +}], consistent with the existence of three conformations in equilibrium, E*, E and E:Na{sup +}, as for human thrombin. Evidence that meizothrombin exists in multiple conformations provides valuable new information for studies of the mechanism of prothrombin activation.« less

Moringa oleifera Lam.: Protease activity against blood coagulation cascade

PubMed Central

Satish, A; Sairam, Sudha; Ahmed, Faiyaz; Urooj, Asna

2012-01-01

Background: The present study evaluated the protease activity of aqueous extracts of Moringa oleifera (Moringaceae) leaf (MOL) and root (MOR). Materials and Methods: Protease activity was assayed using casein, human plasma clot and human fibrinogen as substrates. Results: Caseinolytic activity of MOL was significantly higher (P ≤ 0.05) than that of MOR. Similar observations were found in case of human plasma clot hydrolyzing activity, wherein MOL caused significantly higher (P ≤ 0.05) plasma clot hydrolysis than MOR. Zymographic techniques were used to detect proteolytic enzymes following electrophoretic separation in gels. Further, both the extracts exhibited significant procoagulant activity as reflected by a significant decrease (P ≤ 0.05) in recalcification time, accompanied by fibrinogenolytic and fibrinolytic activities; clotting time was decreased from 180 ± 10 sec to 119 ± 8 sec and 143 ± 10 sec by MOL and MOR, respectively, at a concentration of 2.5 mg/mL. Fibrinogenolytic (human fibrinogen) and fibrinolytic activity (human plasma clot) was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), plate method and colorimetric method. Zymographic profile indicated that both the extracts exerted their procoagulant activity by selectively hydrolyzing Aα and Bβ subunits of fibrinogen to form fibrin clot, thereby exhibiting fibrinogenolytic activity. However, prolonged incubation resulted in degradation of the formed fibrin clot, suggesting fibrinolytic like activity. Conclusions: These findings support the traditional usage of M. oleifera extracts for wound healing. PMID:22224061

Moringa oleifera Lam.: Protease activity against blood coagulation cascade.

PubMed

Satish, A; Sairam, Sudha; Ahmed, Faiyaz; Urooj, Asna

2012-01-01

The present study evaluated the protease activity of aqueous extracts of Moringa oleifera (Moringaceae) leaf (MOL) and root (MOR). Protease activity was assayed using casein, human plasma clot and human fibrinogen as substrates. Caseinolytic activity of MOL was significantly higher (P ≤ 0.05) than that of MOR. Similar observations were found in case of human plasma clot hydrolyzing activity, wherein MOL caused significantly higher (P ≤ 0.05) plasma clot hydrolysis than MOR. Zymographic techniques were used to detect proteolytic enzymes following electrophoretic separation in gels. Further, both the extracts exhibited significant procoagulant activity as reflected by a significant decrease (P ≤ 0.05) in recalcification time, accompanied by fibrinogenolytic and fibrinolytic activities; clotting time was decreased from 180 ± 10 sec to 119 ± 8 sec and 143 ± 10 sec by MOL and MOR, respectively, at a concentration of 2.5 mg/mL. Fibrinogenolytic (human fibrinogen) and fibrinolytic activity (human plasma clot) was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), plate method and colorimetric method. Zymographic profile indicated that both the extracts exerted their procoagulant activity by selectively hydrolyzing Aα and Bβ subunits of fibrinogen to form fibrin clot, thereby exhibiting fibrinogenolytic activity. However, prolonged incubation resulted in degradation of the formed fibrin clot, suggesting fibrinolytic like activity. These findings support the traditional usage of M. oleifera extracts for wound healing.

A Conceptual Model for Teaching the Relationship of Daily Life and Human Environmental Impact to Ecological Function

ERIC Educational Resources Information Center

Wyner, Yael

2013-01-01

In the general activity of daily life, it is easy to miss our dependency on the Earth's ecology. At the same time that people are living apparently separate from the environment, our impact on the Earth is increasing. This study seeks to understand how teachers can bridge this persistent disconnect of daily life from ecology and human impact.…

Reducing Societal Obesity: Establishing a Separate Exercise Model through Studies of Group Behavior.

PubMed

Puterbaugh, J S

2016-01-01

The past 50 years has brought attention to high and increasing levels of human obesity in most of the industrialized world. The medical profession has noticed, has evaluated, and has developed models for studying, preventing, and reversing obesity. The current model prescribes activity in specific quantities such as days, minutes, heart rates, and footfalls. Although decreased levels of activity have come from changes revolving around built environments and social networks, the existing medical model to lower body weights by increasing activity remains individually prescriptive. It is not working. The study of societal obesity precludes the individual and must involve group behavioral studies. Such studies necessitate acquiring separate tools and, therefore, require a significant change in the evaluation and treatment of obesity. Finding groups with common activities and lower levels of obesity would allow the development of new models of land use and encourage active lifestyles through shared interests.

[Study of the antitumor activity of alveolar macrophages after transfected human INF-γ gene].

PubMed

Zhou, Fengli; Bi, Xiaogang; Zhang, Tiantuo; Huang, Jing

2011-05-01

Alveolar macrophages (AMs) activated have the antitumor activity. The interferon-γ (INF-γ) is one of the stimulating factors. INF-γ can enhance the immune function of AMs in vitro. The aim of this study is to investigate the effect of human INF-γ gene on the antitumor activity of AMs when transfected into the alveolar macrophages (AMs) from the patients with lung cancer in vitro. AMs obtained by brochoalveolar lavage were separated and transfected by INF-γ gene. RT-PCR and ELISA were applied to determine whether the transfection was successful. The levels of tumor necrosis factor α (TNF-α), nitric oxide (NO) and interleukin-1 (IL-1) produced by AMs and the killing activity of AMs against L1210 cells was detected respectively. Both RT-PCR and ELISA demonstrated that human INF-γ gene had been successfully transfected into AMs. When transfected by human INF-γ gene, the levels of TNF-α, NO and IL-1 produced by AMs from the patients with lung cancer and the killing activity of AMs against L1210 cells were significantly higher than those of the control groups. Human INF-γ gene can enhance the antitumor activity of AMs when transfected into AMs from the patients with lung cancer.

Cerium and lanthanum-modified, magnetically separable nano-catalysts for water treatment

EPA Science Inventory

Currently, people are exposed to many chemicals in the environment by a variety of chemicals used and produced for anthropogenic activities. Many studies reportadverse effects of chemicals in the environment on the health of humans and animals; such as endocrine disruption, femin...

Different impressions of other agents obtained through social interaction uniquely modulate dorsal and ventral pathway activities in the social human brain.

PubMed

Takahashi, Hideyuki; Terada, Kazunori; Morita, Tomoyo; Suzuki, Shinsuke; Haji, Tomoki; Kozima, Hideki; Yoshikawa, Masahiro; Matsumoto, Yoshio; Omori, Takashi; Asada, Minoru; Naito, Eiichi

2014-09-01

Internal (neuronal) representations in the brain are modified by our experiences, and this phenomenon is not unique to sensory and motor systems. Here, we show that different impressions obtained through social interaction with a variety of agents uniquely modulate activity of dorsal and ventral pathways of the brain network that mediates human social behavior. We scanned brain activity with functional magnetic resonance imaging (fMRI) in 16 healthy volunteers when they performed a simple matching-pennies game with a human, human-like android, mechanical robot, interactive robot, and a computer. Before playing this game in the scanner, participants experienced social interactions with each opponent separately and scored their initial impressions using two questionnaires. We found that the participants perceived opponents in two mental dimensions: one represented "mind-holderness" in which participants attributed anthropomorphic impressions to some of the opponents that had mental functions, while the other dimension represented "mind-readerness" in which participants characterized opponents as intelligent. Interestingly, this "mind-readerness" dimension correlated to participants frequently changing their game tactic to prevent opponents from envisioning their strategy, and this was corroborated by increased entropy during the game. We also found that the two factors separately modulated activity in distinct social brain regions. Specifically, mind-holderness modulated activity in the dorsal aspect of the temporoparietal junction (TPJ) and medial prefrontal and posterior paracingulate cortices, while mind-readerness modulated activity in the ventral aspect of TPJ and the temporal pole. These results clearly demonstrate that activity in social brain networks is modulated through pre-scanning experiences of social interaction with a variety of agents. Furthermore, our findings elucidated the existence of two distinct functional networks in the social human brain. Social interaction with anthropomorphic or intelligent-looking agents may distinctly shape the internal representation of our social brain, which may in turn determine how we behave for various agents that we encounter in our society. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

alpha-Lactalbumin species variation, HAMLET formation, and tumor cell death.

PubMed

Pettersson, Jenny; Mossberg, Ann-Kristin; Svanborg, Catharina

2006-06-23

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex of apo alpha-lactalbumin and oleic acid, formed in casein after low pH treatment of human milk. This study examined if HAMLET-like complexes are present in casein from different species and if isolated alpha-lactalbumin from those species can form such complexes with oleic acid. Casein from human, bovine, equine, and porcine milk was separated by ion exchange chromatography and active complexes were only found in human casein. This was not explained by alpha-lactalbumin sequence variation, as purified bovine, equine, porcine, and caprine alpha-lactalbumins formed complexes with oleic acid with biological activity similar to HAMLET. We conclude that structural variation of alpha-lactalbumins does not preclude the formation of HAMLET-like complexes and that natural HAMLET formation in casein was unique to human milk, which also showed the highest oleic acid content.

Bridging animal and human models of exercise-induced brain plasticity

PubMed Central

Voss, Michelle W.; Vivar, Carmen; Kramer, Arthur F.; van Praag, Henriette

2015-01-01

Significant progress has been made in understanding the neurobiological mechanisms through which exercise protects and restores the brain. In this feature review, we integrate animal and human research, examining physical activity effects across multiple levels of description (neurons up to inter-regional pathways). We evaluate the influence of exercise on hippocampal structure and function, addressing common themes such as spatial memory and pattern separation, brain structure and plasticity, neurotrophic factors, and vasculature. Areas of research focused more within species, such as hippocampal neurogenesis in rodents, also provide crucial insight into the protective role of physical activity. Overall, converging evidence suggests exercise benefits brain function and cognition across the mammalian lifespan, which may translate into reduced risk for Alzheimer’s disease (AD) in humans. PMID:24029446

Stabilization and localization of Xist RNA are controlled by separate mechanisms and are not sufficient for X inactivation.

PubMed

Clemson, C M; Chow, J C; Brown, C J; Lawrence, J B

1998-07-13

These studies address whether XIST RNA is properly localized to the X chromosome in somatic cells where human XIST expression is reactivated, but fails to result in X inactivation (Tinker, A.V., and C.J. Brown. 1998. Nucl. Acids Res. 26:2935-2940). Despite a nuclear RNA accumulation of normal abundance and stability, XIST RNA does not localize in reactivants or in naturally inactive human X chromosomes in mouse/ human hybrid cells. The XIST transcripts are fully stabilized despite their inability to localize, and hence XIST RNA localization can be uncoupled from stabilization, indicating that these are separate steps controlled by distinct mechanisms. Mouse Xist RNA tightly localized to an active X chromosome, demonstrating for the first time that the active X chromosome in somatic cells is competent to associate with Xist RNA. These results imply that species-specific factors, present even in mature, somatic cells that do not normally express Xist, are necessary for localization. When Xist RNA is properly localized to an active mouse X chromosome, X inactivation does not result. Therefore, there is not a strict correlation between Xist localization and chromatin inactivation. Moreover, expression, stabilization, and localization of Xist RNA are not sufficient for X inactivation. We hypothesize that chromosomal association of XIST RNA may initiate subsequent developmental events required to enact transcriptional silencing.

Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans.

PubMed

Cui, Jian; McQuillan, Patrick M; Blaha, Cheryl; Kunselman, Allen R; Sinoway, Lawrence I

2012-08-15

We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P < 0.01) and more sustained MSNA and blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects.

A simplified sheathless cell separation approach using combined gravitational-sedimentation-based prefocusing and dielectrophoretic separation.

PubMed

Luo, Tao; Fan, Lei; Zeng, Yixiao; Liu, Ya; Chen, Shuxun; Tan, Qiulin; Lam, Raymond H W; Sun, Dong

2018-05-04

Prefocusing of the cell mixture is necessary for achieving a high-efficiency and continuous dielectrophoretic (DEP) cell separation. However, prefocusing through sheath flow requires a complex and tedious peripheral system for multi-channel fluid control, hindering the integration of DEP separation systems with other microfluidic functionalities for comprehensive clinical and biological tasks. This paper presented a simplified sheathless cell separation approach that combines gravitational-sedimentation-based sheathless prefocusing and DEP separation methods. Through gravitational sedimentation in a tubing, which was inserted into the inlet of a microfluidic chip with an adjustable steering angle, the cells were focused into a stream at the upstream region of a microchannel prior to separation. Then, a DEP force was applied at the downstream region of the microchannel for the active separation of the cells. Through this combined strategy, the peripheral system for the sheath flow was no longer required, and thus the integration of cell separation system with additional microfluidic functionalities was facilitated. The proposed sheathless scheme focused the mixture of cells with different sizes and dielectric properties into a stream in a wide range of flow rates without changing the design of the microfluidic chip. The DEP method is a label-free approach that can continuously separate cells on the basis of the sizes or dielectric properties of the cells and thus capable of greatly flexible cell separation. The efficiency of the proposed approach was experimentally assessed according to its performance in the separation of human acute monocytic leukemia THP-1 cells from yeast cells with respect to different sizes and THP-1 cells from human acute myelomonocytic leukemia OCI-AML3 cells with respect to different dielectric properties. The experimental results revealed that the separation efficiency of the method can surpass 90% and thus effective in separating cells on the basis of either size or dielectric property.

Purification and Cultivation of Human Pituitary Growth Hormones Secreting Cells

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Todd, P.; Grindeland, R.; Lanham, W.; Morrison, D.

1985-01-01

The rat and human pituitary gland contains a mixture of hormone producing cell types. The separation of cells which make growth hormone (GH) is attempted for the purpose of understanding how the hormone molecule is made within the pituitary cell; what form(s) it takes within the cell; and what form(s) GH assumes as it leaves the cell. Since GH has a number of biological targets (e.g., muscle, liver, bone), the assessment of the activities of the intracellular/extracellular GH by new and sensitive bioassays. GH cells contained in the mixture was separated by free flow electrophoresis. These experiments show that GH cells have different electrophoretic mobilities. This is relevant to NASA since a lack of GH could be a prime causative factor in muscle atrophy. Further, GH has recently been implicated in the etiology of motion sickness in space. Continous flow electrophoresis experiment on STS-8 showed that GH cells could be partially separated in microgravity. However, definitive cell culture studies could not be done due to insufficient cell recoveries.

Separation of granulocytes from whole blood by leukoadhesion, phase 1

NASA Technical Reports Server (NTRS)

1976-01-01

Capillary glass tubes are investigated for the separation and retrieval of large quantities of viable granulocytes and monocytes from whole blood on a continuous basis from a single donor. This effort represented the feasibility demonstration of a three phase program for development of a capillary tube cell separation device. The activity included the analysis and parametric laboratory testing with subscale models required to design a prototype device. Capillary tubes 40 cm long with a nominal 0.030 cm internal diameter yielded the highest total process efficiency. Recovery efficiencies as high as 89% of the adhering cell population were obtained. Granulocyte phagocytosis of latex particles indicated approximately 90% viability. Monocytes recovered from the separation column retained their capability to stimulate human bone marrow colony growth, as demonstrated in an in vitro cell culture assay.

ATM directs DNA damage responses and proteostasis via genetically separable pathways.

PubMed

Lee, Ji-Hoon; Mand, Michael R; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W; Richards, Alicia L; Coon, Joshua J; Paull, Tanya T

2018-01-09

The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated the activation of ATM by DNA damage from that by oxidative stress using separation-of-function mutations. We found that deficient activation of ATM by the Mre11-Rad50-Nbs1 complex and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of a variant ATM incapable of activation by oxidative stress resulted in widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicate ATM in the control of protein homeostasis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rong-Nan Huang; I-Ching Ho; Ling-Hui Yih

Arsenic, strongly associated with increased risks of human cancers, is a potent clastogen in a variety of mammalian cell systems. The effect of sodium arsenite (a trivalent arsenic compound) on chromatid separation was studied in human skin fibroblasts (HFW). Human fibroblasts were arrested in S phase by the aid of serum starvation and aphidicolin blocking and then these cells were allowed to synchronously progress into G2 phase. Treatment of the G2-enriched HFW cells with sodium arsenite (0-200 {mu}M) resulted in arrest of cells in the G2 phase, interference with mitotic division, inhibition of spindle assembly, and induction of chromosome endoreduplicationmore » in their second mitosis. Sodium arsenite treatment also inhibited the activities of serine/threonine protein phosphatases and enhanced phosphorylation levels of a small heat shock protein (HSP27). These results suggest that sodium arsenite may mimic okadaic acid to induce chromosome endoreduplication through its inhibitory effect on protein phosphatase activity. 61 refs., 6 figs., 2 tabs.« less

Human Cortical θ during Free Exploration Encodes Space and Predicts Subsequent Memory

PubMed Central

Snider, Joseph; Plank, Markus; Lynch, Gary; Halgren, Eric

2013-01-01

Spatial representations and walking speed in rodents are consistently related to the phase, frequency, and/or amplitude of θ rhythms in hippocampal local field potentials. However, neuropsychological studies in humans have emphasized the importance of parietal cortex for spatial navigation, and efforts to identify the electrophysiological signs of spatial navigation in humans have been stymied by the difficulty of recording during free exploration of complex environments. We resolved the recording problem and experimentally probed brain activity of human participants who were fully ambulant. On each of 2 d, electroencephalography was synchronized with head and body movement in 13 subjects freely navigating an extended virtual environment containing numerous unique objects. θ phase and amplitude recorded over parietal cortex were consistent when subjects walked through a particular spatial separation at widely separated times. This spatial displacement θ autocorrelation (STAcc) was quantified and found to be significant from 2 to 8 Hz within the environment. Similar autocorrelation analyses performed on an electrooculographic channel, used to measure eye movements, showed no significant spatial autocorrelations, ruling out eye movements as the source of STAcc. Strikingly, the strength of an individual's STAcc maps from day 1 significantly predicted object location recall success on day 2. θ was also significantly correlated with walking speed; however, this correlation appeared unrelated to STAcc and did not predict memory performance. This is the first demonstration of memory-related, spatial maps in humans generated during active spatial exploration. PMID:24048836

Human cortical θ during free exploration encodes space and predicts subsequent memory.

PubMed

Snider, Joseph; Plank, Markus; Lynch, Gary; Halgren, Eric; Poizner, Howard

2013-09-18

Spatial representations and walking speed in rodents are consistently related to the phase, frequency, and/or amplitude of θ rhythms in hippocampal local field potentials. However, neuropsychological studies in humans have emphasized the importance of parietal cortex for spatial navigation, and efforts to identify the electrophysiological signs of spatial navigation in humans have been stymied by the difficulty of recording during free exploration of complex environments. We resolved the recording problem and experimentally probed brain activity of human participants who were fully ambulant. On each of 2 d, electroencephalography was synchronized with head and body movement in 13 subjects freely navigating an extended virtual environment containing numerous unique objects. θ phase and amplitude recorded over parietal cortex were consistent when subjects walked through a particular spatial separation at widely separated times. This spatial displacement θ autocorrelation (STAcc) was quantified and found to be significant from 2 to 8 Hz within the environment. Similar autocorrelation analyses performed on an electrooculographic channel, used to measure eye movements, showed no significant spatial autocorrelations, ruling out eye movements as the source of STAcc. Strikingly, the strength of an individual's STAcc maps from day 1 significantly predicted object location recall success on day 2. θ was also significantly correlated with walking speed; however, this correlation appeared unrelated to STAcc and did not predict memory performance. This is the first demonstration of memory-related, spatial maps in humans generated during active spatial exploration.

Aerial ULV application of Dibrom against Aedes aegypti in simulated urban and rural residences

USDA-ARS?s Scientific Manuscript database

Reaching endophilic Aedes aegypti mosquito vectors of dengue located in human residences with aerial ULV pesticide applications is a prominent complication in operational wide area public health mosquito control activities. We conducted separate trials with a military C-130 fixed wing aircraft fitte...

Amygdala activity at encoding correlated with long-term, free recall of emotional information.

PubMed

Cahill, L; Haier, R J; Fallon, J; Alkire, M T; Tang, C; Keator, D; Wu, J; McGaugh, J L

1996-07-23

Positron emission tomography of cerebral glucose metabolism in adult human subjects was used to investigate amygdaloid complex (AC) activity associated with the storage of long-term memory for emotionally arousing events. Subjects viewed two videos (one in each of two separate positron emission tomography sessions, separated by 3-7 days) consisting either of 12 emotionally arousing film clips ("E" film session) or of 12 relatively emotionally neutral film clips ("N" film session), and rated their emotional reaction to each film clip immediately after viewing it. Three weeks after the second session, memory for the videos was assessed in a free recall test. As expected, the subjects' average emotional reaction to the E films was higher than that for the N films. In addition, the subjects recalled significantly more E films than N films. Glucose metabolic rate of the right AC while viewing the E films was highly correlated with the number of E films recalled. AC activity was not significantly correlated with the number of N films recalled. The findings support the view derived from both animal and human investigations that the AC is selectively involved with the formation of enhanced long-term memory associated with emotionally arousing events.

Cryptolepine, isolated from Sida acuta, sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis.

PubMed

Ahmed, Firoj; Toume, Kazufumi; Ohtsuki, Takashi; Rahman, Mahmudur; Sadhu, Samir Kumar; Ishibashi, Masami

2011-01-01

Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2-3). Compound 1 showed strong activity in overcoming TRAIL-resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL-induced apoptosis at the aforementioned concentrations. Copyright © 2010 John Wiley & Sons, Ltd.

Limited communication capacity unveils strategies for human interaction

NASA Astrophysics Data System (ADS)

Miritello, Giovanna; Lara, Rubén; Cebrian, Manuel; Moro, Esteban

2013-06-01

Connectivity is the key process that characterizes the structural and functional properties of social networks. However, the bursty activity of dyadic interactions may hinder the discrimination of inactive ties from large interevent times in active ones. We develop a principled method to detect tie de-activation and apply it to a large longitudinal, cross-sectional communication dataset (~19 months, ~20 million people). Contrary to the perception of ever-growing connectivity, we observe that individuals exhibit a finite communication capacity, which limits the number of ties they can maintain active in time. On average men display higher capacity than women, and this capacity decreases for both genders over their lifespan. Separating communication capacity from activity reveals a diverse range of tie activation strategies, from stable to exploratory. This allows us to draw novel relationships between individual strategies for human interaction and the evolution of social networks at global scale.

Limited communication capacity unveils strategies for human interaction

PubMed Central

Miritello, Giovanna; Lara, Rubén; Cebrian, Manuel; Moro, Esteban

2013-01-01

Connectivity is the key process that characterizes the structural and functional properties of social networks. However, the bursty activity of dyadic interactions may hinder the discrimination of inactive ties from large interevent times in active ones. We develop a principled method to detect tie de-activation and apply it to a large longitudinal, cross-sectional communication dataset (≈19 months, ≈20 million people). Contrary to the perception of ever-growing connectivity, we observe that individuals exhibit a finite communication capacity, which limits the number of ties they can maintain active in time. On average men display higher capacity than women, and this capacity decreases for both genders over their lifespan. Separating communication capacity from activity reveals a diverse range of tie activation strategies, from stable to exploratory. This allows us to draw novel relationships between individual strategies for human interaction and the evolution of social networks at global scale. PMID:23739519

Biochemical assays on plasminogen activators and hormones from kidney sources

NASA Technical Reports Server (NTRS)

Barlow, Grant H.; Lewis, Marian L.; Morrison, Dennis R.

1988-01-01

Investigations were established for the purpose of analyzing the conditioned media from human embryonic kidney cell subpopulations separated in space by electrophoresis. This data is based on the experiments performed on STS-8 on the continuous flow electrophoresis system. The primary biological activity that was analyzed was plasminogen activator activity, but some assays for erythropoeitin and human granulocyte colony stimulating activity were also performed. It is concluded that a battery of assays are required to completely define the plasminogen activator profile of a conditioned media from cell culture. Each type of assay measures different parts of the mixture and are influenced by different parameters. The functional role of each assay is given along with an indication of which combination of assays are required to answer specific questions. With this type of information it is possible by combinations of assays with mathematical analysis to pinpoint a specific component of the system.

[Novel bidirectional promoter from human genome].

PubMed

Orekhova, A S; Sverdlova, P S; Spirin, P V; Leonova, O G; Popenko, V I; Prasolov, V S; Rubtsov, P M

2011-01-01

In human and other mammalian genomes a number of closely linked gene pairs transcribed in opposite directions are found. According to bioinformatic analysis up to 10% of human genes are arranged in this way. In present work the fragment of human genome was cloned that separates genes localized at 2p13.1 and oriented "head-to-head", coding for hypothetical proteins with unknown functions--CCDC (Coiled Coil Domain Containing) 142 and TTC (TetraTricopeptide repeat Containing) 31. Intergenic CCDC142-TTC31 region overlaps with CpG-island and contains a number of potential binding sites for transcription factors. This fragment functions as bidirectional promoter in the system ofluciferase reporter gene expression upon transfection of human embryonic kidney (HEK293) cells. The vectors containing genes of two fluorescent proteins--green (EGFP) and red (DsRed2) in opposite orientations separated by the fragment of CCDC142-TTC31 intergenic region were constructed. In HEK293 cells transfected with these vectors simultaneous expression of two fluorescent proteins is observed. Truncated versions of intergenic region were obtained and their promoter activity measured. Minimal promoter fragment contains elements Inr, BRE, DPE characteristic for TATA-less promoters. Thus, from the human genome the novel bidirectional promoter was cloned that can be used for simultaneous constitutive expression of two genes in human cells.

Short separation channel location impacts the performance of short channel regression in NIRS

PubMed Central

Gagnon, Louis; Cooper, Robert J.; Yücel, Meryem A.; Perdue, Katherine L.; Greve, Douglas N.; Boas, David A.

2011-01-01

Near-Infrared Spectroscopy (NIRS) allows the recovery of cortical oxy-and deoxyhemoglobin changes associated with evoked brain activity. NIRS is a back-reflection measurement making it very sensitive to the superficial layers of the head, i.e. the skin and the skull, where systemic interference occurs. As a result, the NIRS signal is strongly contaminated with systemic interference of superficial origin. A recent approach to overcome this problem has been the use of additional short source-detector separation optodes as regressors. Since these additional measurements are mainly sensitive to superficial layers in adult humans, they can be used to remove the systemic interference present in longer separation measurements, improving the recovery of the cortical hemodynamic response function (HRF). One question that remains to answer is whether or not a short separation measurement is required in close proximity to each long separation NIRS channel. Here, we show that the systemic interference occurring in the superficial layers of the human head is inhomogeneous across the surface of the scalp. As a result, the improvement obtained by using a short separation optode decreases as the relative distance between the short and the long measurement is increased. NIRS data was acquired on 6 human subjects both at rest and during a motor task consisting of finger tapping. The effect of distance between the short and the long channel was first quantified by recovering a synthetic hemodynamic response added over the resting-state data. The effect was also observed in the functional data collected during the finger tapping task. Together, these results suggest that the short separation measurement must be located as close as 1.5 cm from the standard NIRS channel in order to provide an improvement which is of practical use. In this case, the improvement in Contrast-to-Noise Ratio (CNR) compared to a standard General Linear Model (GLM) procedure without using any small separation optode reached 50 % for HbO and 100 % for HbR. Using small separations located farther than 2 cm away resulted in mild or negligible improvements only. PMID:21945793

Space station proximity operations windows: Human factors design guidelines

NASA Technical Reports Server (NTRS)

Haines, Richard F.

1987-01-01

Proximity operations refers to all activities outside the Space Station which take place within a 1-km radius. Since there will be a large number of different operations involving manned and unmanned vehicles, single- and multiperson crews, automated and manually controlled flight, a wide variety of cargo, and construction/repair activities, accurate and continuous human monitoring of these operations from a specially designed control station on Space Station will be required. Total situational awareness will be required. This paper presents numerous human factors design guidelines and related background information for control windows which will support proximity operations. Separate sections deal with natural and artificial illumination geometry; all basic rendezvous vector approaches; window field-of-view requirements; window size; shape and placement criteria; window optical characteristics as they relate to human perception; maintenance and protection issues; and a comprehensive review of windows installed on U.S. and U.S.S.R. manned vehicles.

Combined activity of post-exercise concentrations of NA and eHsp72 on human neutrophil function: role of cAMP.

PubMed

Giraldo, Esther; Hinchado, María D; Ortega, Eduardo

2013-09-01

Extracellular heat shock proteins of 72 kDa (eHsp72) and noradrenaline (NA) can act as "danger signals" during exercise-induced stress by activating neutrophil function (chemotaxis, phagocytosis, and fungicidal capacity). In addition, post-exercise concentrations of NA increase the expression and release of Hsp72 by human neutrophils, and adrenoreceptors and cAMP are involved in the stimulation of neutrophils by eHsp72. This suggests an interaction between the two molecules in the modulation of neutrophils during exercise-induced stress. Given this context, the aim of the present investigation was to study the combined activity of post-exercise circulating concentrations of NA and eHsp72 on the neutrophil phagocytic process, and to evaluate the role of cAMP as intracellular signal in these effects. Results showed an accumulative stimulation of chemotaxis induced by NA and eHsp72. However, while NA and eHsp72, separately, stimulate the phagocytosis and fungicidal activity of neutrophils, when they act together they do not modify these capacities of neutrophils. Similarly, post-exercise concentrations of NA and eHsp72 separately increased the intracellular level of cAMP, but NA and eHsp72 acting together did not modify the intracellular concentration of cAMP. These results confirm that cAMP can be involved in the autocrine/paracrine physiological regulation of phagocytosis and fungicidal capacity of human neutrophils mediated by NA and eHsp72 in the context of exercise-induced stress. Copyright © 2013 Wiley Periodicals, Inc.

Bioactivities of anastasia black (Russian sweet pepper).

PubMed

Shirataki, Yoshiaki; Kawase, Masami; Sakagami, Hiroshi; Nakashima, Hideki; Tani, Satoru; Tanaka, Toru; Sohara, Yoshitaka; Schelz, Zsuzsanna; Molnar, Joseph; Motohashi, Noboru

2005-01-01

Anastasia Black (Russian sweet pepper) of Capsicum annuum L. var. angulosum Mill. (Solanaceae) was successively extracted with hexane, acetone, methanol and 70% methanol, and the extracts were further separated into a total of twenty-three fractions by silica gel or octadecylsilane (ODS; C18) column chromatography. These extracts and fractions were investigated for their cytotoxicity, anti-human immunodeficiency virus (HIV), anti-Helicobacter pylori (H. pylori), urease inhibition and multidrug resistance (MDR) reversal activity. Some fractions of hexane and acetone extracts showed higher cytotoxic activity against three human oral tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG) than against three normal human oral cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF), suggesting a tumor-specific cytotoxic activity. No fractions displayed anti-HIV activity, but some hydrophobic fractions showed higher anti-H. pylori activity, urease inhibition activity and MDR reversal activity. The higher MDR activity of these fractions against MDR gene-transfected L5178 mouse lymphoma T cells may possibly be due to their higher content of carotene or polyphenol. These data suggest that Anastasia Black should be further investigated as a potent supplement for cancer chemotherapy.

Timing of target discrimination in human frontal eye fields.

PubMed

O'Shea, Jacinta; Muggleton, Neil G; Cowey, Alan; Walsh, Vincent

2004-01-01

Frontal eye field (FEF) neurons discharge in response to behaviorally relevant stimuli that are potential targets for saccades. Distinct visual and motor processes have been dissociated in the FEF of macaque monkeys, but little is known about the visual processing capacity of FEF in humans. We used double-pulse transcranial magnetic stimulation [(d)TMS] to investigate the timing of target discrimination during visual conjunction search. We applied dual TMS pulses separated by 40 msec over the right FEF and vertex. These were applied in five timing conditions to sample separate time windows within the first 200 msec of visual processing. (d)TMS impaired search performance, reflected in reduced d' scores. This effect was limited to a time window between 40 and 80 msec after search array onset. These parameters correspond with single-cell activity in FEF that predicts monkeys' behavioral reports on hit, miss, false alarm, and correct rejection trials. Our findings demonstrate a crucial early role for human FEF in visual target discrimination that is independent of saccade programming.

Kidney cell electrophoresis in space flight: Rationale, methods, results and flow cytometry applications

NASA Technical Reports Server (NTRS)

Todd, P.; Morrison, Dennis R.; Barlow, Grant H.; Lewis, Marian L.; Lanham, J. W.; Cleveland, C.; Williams, K.; Kunze, M. E.; Goolsby, C. L.

1988-01-01

Cultures of human embryonic kidney cells consistently contain an electrophoretically separable subpopulation of cells that produce high levels of urokinase and have an electrophoretic mobility about 85 percent as high as that of the most mobile human embryonic kidney cells. This subpopulation is rich in large epithelioid cells that have relatively little internal structure. When resolution and throughput are adequate, free fluid electrophoresis can be used to isolate a broad band of low mobility cells which also produces high levels of plasminogen activators (PAs). In the course of performing this, it was discovered that all electrophoretic subpopulations of cultured human embryonic kidney cells produce some PAs and that separate subpopulations produce high quantities of different types of PA's. This information and the development of sensitive assays for this project have provided new insights into cell secretion mechanisms related to fibrinolysis. These advances would probably not have been made without the NASA program to explore fundamental questions of free fluid electrophoresis in space.

A validated HPLC-MS/MS assay for quantifying unstable pharmacologically active metabolites of clopidogrel in human plasma: application to a clinical pharmacokinetic study.

PubMed

Furlong, Michael T; Savant, Ishani; Yuan, Moucun; Scott, Laura; Mylott, William; Mariannino, Thomas; Kadiyala, Pathanjali; Roongta, Vikram; Arnold, Mark E

2013-05-01

Clopidogrel is prescribed for the treatment of Acute Coronary Syndrome and recent myocardial infarction, recent stroke, or established peripheral arterial disease. A sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay was developed and validated to enable reliable quantification of four diastereomeric and chemically reactive thiol metabolites, two of which are pharmacologically active, in human plasma. The metabolites were stabilized by alkylation of their reactive thiol moieties with 2-bromo-3'-methoxyacetophenone (MPB). Following organic solvent mediated-protein precipitation in a 96-well plate format, chromatographic separation was achieved by gradient elution on an Ascentis Express RP-amide column. Chromatographic conditions were optimized to ensure separation of the four derivatized active metabolites. Derivatized metabolites and stable isotope-labeled internal standards were detected by positive ion electrospray tandem mass spectrometry. The HPLC-MS/MS assay was validated over concentration ranges of 0.125-125 ng/mL for metabolites H1-H3 and 0.101-101 ng/mL for H4. Intra- and inter-assay precision values for replicate quality control samples were within 14.3% for all analytes during the assay validation. Mean quality control accuracy values were within ±6.3% of nominal values for all analytes. Assay recoveries were high (>79%). The four derivatized analytes were stable in human blood for at least 2 h at room temperature and on ice. The analytes were also stable in human plasma for at least 25 h at room temperature, 372 days at -20 °C and -70 °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of all four thiol metabolites in human plasma in support of a human pharmacokinetic study. Copyright © 2013 Elsevier B.V. All rights reserved.

A pyrogen derived from human white cells which is active in mice.

PubMed Central

Gordon, A. H.; Parker, I. D.

1980-01-01

An endogenous pyrogen smaller in molecular size than that previously obtained from human white cells has been found in supernatants of these cells after uptake of zymosan and incubation for 18 h. The new pyrogen after separation from other pyrogens which are produced at the same time has been found to produce fever in mice but not in rabbits. Because it is not formed if cycloheximide is present and is inactivated by leucine aminopeptidase, it is believed to be a peptide. PMID:7448120

Identification of 6-methylsulfinylhexyl isothiocyanate as an apoptosis-inducing component in wasabi.

PubMed

Watanabe, Makoto; Ohata, Masahiko; Hayakawa, Sumio; Isemura, Mamoru; Kumazawa, Shigenori; Nakayama, Tsutomu; Furugori, Michiyo; Kinae, Naohide

2003-03-01

The ethanol extract from Japanese horseradish wasabi was found to inhibit cell proliferation in human monoblastic leukemia U937 cells by inducing apoptotic cell death. Separation by methods including silica gel chromatography and preparative HPLC gave an active compound, which was identified as 6-methylsulfinylhexyl isothiocyanate (6-HITC). Several lines of evidence indicated that 6-HITC induced apoptosis in U937 cells and human stomach cancer MKN45 cells. Thus, 6-HITC is potentially useful as a natural anti-cancer agent.

Targeting of the MUC1-C Oncoprotein in Colitis-Associated Colorectal Cancer

DTIC Science & Technology

2014-11-01

separated by infiltrates of inflammatory cells and the presence of crypt abscess (lower left panel). With progression to dysplasia, the crypts are...Rajabi, H, et al., MUC1-C oncoprotein induces TCF7L2 activation and promotes cyclin D1 expression in human breast cancer cells. J Biol Chem, 2012

76 FR 58321 - Privacy Act of 1974; Publication of Notice of Systems of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-20

... concerning aliens. Department of Health and Human Services--For locations of parents pursuant to the Child... sources of information include the Report of Separation From Active Duty (DD Form 214), referral documents... parents pursuant to the Child Support Enforcement Act. State and Local Governments--To provide data that...

[Evaluation of the total biological activity and allergenic composition of allergenic extracts].

PubMed

Lombardero, M; González, R; Duffort, O; Juan, F; Ayuso, R; Ventas, P; Cortés, C; Carreira, J

1986-01-01

In the present study, a complete procedure is presented in order to standardize allergenic extracts, the meaning of which is the measurement of the total allergenic activity and the determination of the allergenic composition. The measurement of the biological activity comprises 2 steps: Preparation of Reference Extracts and determination of their "in vivo" activity. Evaluation of the total allergenic activity of extracts for clinical use. Reference extracts were prepared from the main allergens and their "in vivo" biological activity was determined by a quantitative skin prick test in a sample of at least 30 allergic patients. By definition, the protein concentration of Reference Extract that produces, in the allergic population, a geometric mean wheal of 75 mm.2 has an activity of 100 biological units (BUs). The determination of the biological activity of a problem extract is made by RAST inhibition. The sample is compared with the corresponding Reference Extract by this technique and, from this comparison, it is possible to quantify the activity of the problem extract in biologic units (BUs) with clinical significance. Likewise, different techniques have been used to determine the allergenic composition of extracts. These techniques comprise 2 steps: Separation of the components of the extract. Identification of the components that bind specific human IgE. The separation of the components of the extract has been carried out by isoelectric focusing (IEF) and electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE). In order to identify the allergenic components, an immunoblotting technique has been employed. The separated components in the IEF gel or SDS-PAGE gel are transferred to a nitrocellulose sheet and later on, this membrane is overlaid with a serum pool from allergic patients and a mouse monoclonal anti-human IgE, labelled with 125I. Finally, the autoradiography of the nitrocellulose membrane is obtained. In this way it is possible to compare the allergenic composition of an extract with the corresponding Reference Extract and so to employ for clinical use only those extracts with the right allergenic composition.

An Adaptive S-Method to Analyze Micro-Doppler Signals for Human Activity Classification

PubMed Central

Yang, Chao; Xia, Yuqing; Ma, Xiaolin; Zhang, Tao; Zhou, Zhou

2017-01-01

In this paper, we propose the multiwindow Adaptive S-method (AS-method) distribution approach used in the time-frequency analysis for radar signals. Based on the results of orthogonal Hermite functions that have good time-frequency resolution, we vary the length of window to suppress the oscillating component caused by cross-terms. This method can bring a better compromise in the auto-terms concentration and cross-terms suppressing, which contributes to the multi-component signal separation. Finally, the effective micro signal is extracted by threshold segmentation and envelope extraction. To verify the proposed method, six states of motion are separated by a classifier of a support vector machine (SVM) trained to the extracted features. The trained SVM can detect a human subject with an accuracy of 95.4% for two cases without interference. PMID:29186075

An Adaptive S-Method to Analyze Micro-Doppler Signals for Human Activity Classification.

PubMed

Li, Fangmin; Yang, Chao; Xia, Yuqing; Ma, Xiaolin; Zhang, Tao; Zhou, Zhou

2017-11-29

In this paper, we propose the multiwindow Adaptive S-method (AS-method) distribution approach used in the time-frequency analysis for radar signals. Based on the results of orthogonal Hermite functions that have good time-frequency resolution, we vary the length of window to suppress the oscillating component caused by cross-terms. This method can bring a better compromise in the auto-terms concentration and cross-terms suppressing, which contributes to the multi-component signal separation. Finally, the effective micro signal is extracted by threshold segmentation and envelope extraction. To verify the proposed method, six states of motion are separated by a classifier of a support vector machine (SVM) trained to the extracted features. The trained SVM can detect a human subject with an accuracy of 95.4% for two cases without interference.

An innovative cascade system for simultaneous separation of multiple cell types.

PubMed

Pierzchalski, Arkadiusz; Mittag, Anja; Bocsi, Jozsef; Tarnok, Attila

2013-01-01

Isolation of different cell types from one sample by fluorescence activated cell sorting is standard but expensive and time consuming. Magnetic separation is more cost effective and faster by but requires substantial effort. An innovative pluriBead-cascade cell isolation system (pluriSelect GmbH, Leipzig, Germany) simultaneously separates two or more different cell types. It is based on antibody-mediated binding of cells to beads of different size and their isolation with sieves of different mesh-size. For the first time, we validated the pluriSelect system for simultaneous separation of CD4+- and CD8+-cells from human EDTA-blood samples. Results were compared with those obtained by magnetic activated cell sorting (MACS; two steps -first isolation of CD4+, then restaining of the residual cell suspension with anti-human CD8+ MACS antibody followed by the second isolation). pluriSelect separation was done in whole blood, MACS separation on density gradient isolated mononuclear cells. Isolated and residual cells were immunophenotyped by 7-color 9-marker panel (CD3; CD16/56; CD4; CD8; CD14; CD19; CD45; HLA-DR) using flow cytometry. Cell count, purity, yield and viability (7-AAD exclusion) were determined. There were no significant differences between both systems regarding purity (MACS (median[range]: 92.4% [91.5-94.9] vs. pluriSelect 95% [94.9-96.8])) of CD4+ cells, however CD8+ isolation showed lower purity by MACS (74.8% [67.6-77.9], pluriSelect 89.9% [89.0-95.7]). Yield was not significantly different for CD4 (MACS 58.5% [54.1-67.5], pluriSelect 67.9% [56.8-69.8]) and for CD8 (MACS 57.2% [41.3-72.0], pluriSelect 67.2% [60.0-78.5]). Viability was slightly higher with MACS for CD4+ (98.4% [97.8-99.0], pluriSelect 94.1% [92.1-95.2]) and for CD8+-cells (98.8% [98.3-99.1], pluriSelect 86.7% [84.2-89.9]). pluriSelect separation was substantially faster than MACS (1h vs. 2.5h) and no pre-enrichment steps were necessary. In conclusion, pluriSelect is a fast, simple and gentle system for efficient simultaneous separation of two and more cell subpopulation directly from whole blood and provides a simple alternative to magnetic separation.

Unmanned Aircraft Systems Human-in-the-Loop Controller and Pilot Acceptability Study: Collision Avoidance, Self-Separation, and Alerting Times (CASSAT)

NASA Technical Reports Server (NTRS)

Comstock, James R., Jr.; Ghatas, Rania W.; Vincent, Michael J.; Consiglio, Maria C.; Munoz, Cesar; Chamberlain, James P.; Volk, Paul; Arthur, Keith E.

2016-01-01

The Federal Aviation Administration (FAA) has been mandated by the Congressional funding bill of 2012 to open the National Airspace System (NAS) to Unmanned Aircraft Systems (UAS). With the growing use of unmanned systems, NASA has established a multi-center "UAS Integration in the NAS" Project, in collaboration with the FAA and industry, and is guiding its research efforts to look at and examine crucial safety concerns regarding the integration of UAS into the NAS. Key research efforts are addressing requirements for detect-and-avoid (DAA), self-separation (SS), and collision avoidance (CA) technologies. In one of a series of human-in-the-loop experiments, NASA Langley Research Center set up a study known as Collision Avoidance, Self-Separation, and Alerting Times (CASSAT). The first phase assessed active air traffic controller interactions with DAA systems and the second phase examined reactions to the DAA system and displays by UAS Pilots at a simulated ground control station (GCS). Analyses of the test results from Phase I and Phase II are presented in this paper. Results from the CASSAT study and previous human-in-the-loop experiments will play a crucial role in the FAA's establishment of rules, regulations, and procedures to safely, efficiently, and effectively integrate UAS into the NAS.

An active second dihydrofolate reductase enzyme is not a feature of rat and mouse, but they do have activity in their mitochondria.

PubMed

Hughes, Linda; Carton, Robert; Minguzzi, Stefano; McEntee, Gráinne; Deinum, Eva E; O'Connell, Mary J; Parle-McDermott, Anne

2015-07-08

The identification of a second functional dihydrofolate reductase enzyme in humans, DHFRL1, led us to consider whether this is also a feature of rodents. We demonstrate that dihydrofolate reductase activity is also a feature of the mitochondria in both rat and mouse but this is not due to a second enzyme. While our phylogenetic analysis revealed that RNA-mediated DHFR duplication events did occur across the mammal tree, the duplicates in brown rat and mouse are likely to be processed pseudogenes. Humans have evolved the need for two separate enzymes while laboratory rats and mice have just one. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Inhibition of human polymorphonuclear leukocyte function by components of human colostrum and mature milk.

PubMed

Pickering, L K; Cleary, T G; Caprioli, R M

1983-04-01

To compare the effect of human colostrum (days 1 to 3 postpartum) and mature milk (days 170 +/- 24 postpartum) on the function of polymorphonuclear leukocytes (PMNL), Ficoll-Hypaque-separated PMNL from the blood of 60 healthy volunteers were incubated with whole colostrum, colostral lipid, and colostral aqueous phase from 30 mothers, or with mature whole milk and its separated components from 30 mothers, and tested for resting and zymosan-stimulated oxidative metabolism, functional activity, and the presence of Fc receptors. Stimulated oxygen consumption, quantitative nitroblue tetrazolium dye reduction, [1-(14)C]glucose utilization, and Fc receptors were significantly (P < 0.05 to P < 0.001) less in PMNL exposed to whole human colostrum or colostral lipid than in non-lipid-exposed cells or cells exposed to the aqueous phase of colostrum. In contrast, PMNL exposed to whole mature milk or to its lipid or aqueous phase caused no significant decrease in any of these parameters when compared to nonexposed cells. In assays of phagocytosis, colostral PMNL or blood PMNL exposed to colostral lipid had a significant (P < 0.001) decrease in their ability to ingest [methyl-(3)H]thymidine-labeled Staphylococcus aureus when compared to non-lipid-exposed PMNL. Blood PMNL exposed to lipid from mature milk had no decrease in ability to ingest S. aureus. Analysis of total lipid and total and individual fatty acid content revealed a uniform increase in all components in mature milk when compared to colostrum. Lipid or lipid-soluble material present in human colostrum but not mature milk causes inhibition of phagocytosis and respiratory burst-related activities of PMNL.

Proteome profile and biological activity of caprine, bovine and human milk fat globules.

PubMed

Spertino, Stefano; Cipriani, Valentina; De Angelis, Chiara; Giuffrida, Maria Gabriella; Marsano, Francesco; Cavaletto, Maria

2012-04-01

Upon combining bidimensional electrophoresis with monodimensional separation, a more comprehensive analysis of the milk fat globule membrane has been obtained. The proteomic profile of caprine milk fat globules revealed the presence of butyrophilin, lactadherin and perilipin as the major proteins, they were also associated to bovine and human milk fat globule membranes. Xanthine dehydrogenase/oxidase has been detected only in monodimensional gels. Biological activity of milk fat globules has been evaluated in Caco2-cells, as a representative model of the intestinal barrier. The increase of cell viability was indicative of a potential nutraceutical role for the whole milk fat globule, suggesting a possible employment in milk formula preparation.

Damaging effects of Clostridium perfringens delta toxin on blood platelets and their relevance to ganglioside GM2.

PubMed

Jolivet-Reynaud, C; Launay, J M; Alouf, J E

1988-04-01

The lytic effect of Clostridium perfringens delta toxin was investigated on goat, human, rabbit, and guinea pig platelets. In contrast to erythrocytes from the latter three species, which are insensitive to the toxin, the platelets were equally lysed by the same amount of toxin. These results suggest the presence of GM2 or GM2-like ganglioside(s) as a specific recognition site of the toxin on platelet plasmic membrane as previously established for sensitive erythrocytes. Plasmic membrane damage of human platelets was evidenced by the release of entrapped alpha-[14C]aminoisobutyric acid used as a cytoplasmic marker. The specific binding of hemolytically active 125I-delta toxin by human and rabbit platelets was practically identical, dose dependent, and inhibitable by GM2. Labeled toxin was also bound by various subcellular organelles separated from rabbit platelets except the 5-hydroxytryptamine (5-HT)-containing dense bodies, suggesting the absence or inaccessibility of GM2 on the surface of the latter organelles. This result correlates with the low amounts of 5-[3H]HT liberated after platelet challenge with delta toxin whereas this mediator was massively liberated upon lysis by the sulfhydryl-activated toxin alveolysin. The levels of M and P forms of phenol sulfotransferase (PST), involved in 5-HT catabolism, were determined in human platelet lysates after challenge with delta toxin, alveolysin, and other disruptive treatments. The low PST-M activities detected after lysis by delta toxin suggest that this isoenzyme is very likely associated to dense bodies in contrast to PST-P which is cytoplasmic. Platelet lysis by the toxin allows easy separation of these organelles.

Pattern Analyses Reveal Separate Experience-Based Fear Memories in the Human Right Amygdala.

PubMed

Braem, Senne; De Houwer, Jan; Demanet, Jelle; Yuen, Kenneth S L; Kalisch, Raffael; Brass, Marcel

2017-08-23

Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US) is often assumed to be fundamentally different from learning fear via instructions. An open question is whether fear-related brain areas respond differently to experienced CS-US contingencies than to merely instructed CS-US contingencies. Here, we contrasted two experimental conditions where subjects were instructed to expect the same CS-US contingencies while only one condition was characterized by prior experience with the CS-US contingency. Using multivoxel pattern analysis of fMRI data, we found CS-related neural activation patterns in the right amygdala (but not in other fear-related regions) that dissociated between whether a CS-US contingency had been instructed and experienced versus merely instructed. A second experiment further corroborated this finding by showing a category-independent neural response to instructed and experienced, but not merely instructed, CS presentations in the human right amygdala. Together, these findings are in line with previous studies showing that verbal fear instructions have a strong impact on both brain and behavior. However, even in the face of fear instructions, the human right amygdala still shows a separable neural pattern response to experience-based fear contingencies. SIGNIFICANCE STATEMENT In our study, we addressed a fundamental problem of the science of human fear learning and memory, namely whether fear learning via experience in humans relies on a neural pathway that can be separated from fear learning via verbal information. Using two new procedures and recent advances in the analysis of brain imaging data, we localized purely experience-based fear processing and memory in the right amygdala, thereby making a direct link between human and animal research. Copyright © 2017 the authors 0270-6474/17/378116-15$15.00/0.

Quantum design of photosynthesis for bio-inspired solar-energy conversion.

PubMed

Romero, Elisabet; Novoderezhkin, Vladimir I; van Grondelle, Rienk

2017-03-15

Photosynthesis is the natural process that converts solar photons into energy-rich products that are needed to drive the biochemistry of life. Two ultrafast processes form the basis of photosynthesis: excitation energy transfer and charge separation. Under optimal conditions, every photon that is absorbed is used by the photosynthetic organism. Fundamental quantum mechanics phenomena, including delocalization, underlie the speed, efficiency and directionality of the charge-separation process. At least four design principles are active in natural photosynthesis, and these can be applied practically to stimulate the development of bio-inspired, human-made energy conversion systems.

Impact of climate variability and anthropogenic activity on streamflow in the Three Rivers Headwater Region, Tibetan Plateau, China

NASA Astrophysics Data System (ADS)

Jiang, Chong; Li, Daiqing; Gao, Yanni; Liu, Wenfeng; Zhang, Linbo

2017-07-01

Under the impacts of climate variability and human activities, there is violent fluctuation for streamflow in the large basins in China. Therefore, it is crucial to separate the impacts of climate variability and human activities on streamflow fluctuation for better water resources planning and management. In this study, the Three Rivers Headwater Region (TRHR) was chosen as the study area. Long-term hydrological data for the TRHR were collected in order to investigate the changes in annual runoff during the period of 1956-2012. The nonparametric Mann-Kendall test, moving t test, Pettitt test, Mann-Kendall-Sneyers test, and the cumulative anomaly curve were used to identify trends and change points in the hydro-meteorological variables. Change point in runoff was identified in the three basins, which respectively occurred around the years 1989 and 1993, dividing the long-term runoff series into a natural period and a human-induced period. Then, the hydrologic sensitivity analysis method was employed to evaluate the effects of climate variability and human activities on mean annual runoff for the human-induced period based on precipitation and potential evapotranspiration. In the human-induced period, climate variability was the main factor that increased (reduced) runoff in LRB and YARB (YRB) with contribution of more than 90 %, while the increasing (decreasing) percentage due to human activities only accounted for less than 10 %, showing that runoff in the TRHR is more sensitive to climate variability than human activities. The intra-annual distribution of runoff shifted gradually from a double peak pattern to a single peak pattern, which was mainly influenced by atmospheric circulation in the summer and autumn. The inter-annual variation in runoff was jointly controlled by the East Asian monsoon, the westerly, and Tibetan Plateau monsoons.

Development of a sliding mode control model for quiet upright stance.

PubMed

Zhang, Hongbo; Nussbaum, Maury A; Agnew, Michael J

2016-02-01

Human upright stance appears maintained or controlled intermittently, through some combination of passive and active ankle torques, respectively representing intrinsic and contractile contributions of the ankle musculature. Several intermittent postural control models have been proposed, though it has been challenging to accurately represent actual kinematics and kinetics and to separately estimate passive and active ankle torque components. Here, a simplified single-segment, 2D (sagittal plane) sliding mode control model was developed for application to track kinematics and kinetics during upright stance. The model was implemented and evaluated using previous experimental data consisting of whole body angular kinematics and ankle torques. Tracking errors for the whole-body center-of-mass (COM) angle and angular velocity, as well as ankle torque, were all within ∼10% of experimental values, though tracking performance for COM angular acceleration was substantially poorer. The model also enabled separate estimates of the contributions of passive and active ankle torques, with overall contributions estimated here to be 96% and 4% of the total ankle torque, respectively. Such a model may have future utility in understanding human postural control, though additional work is needed, such as expanding the model to multiple segments and to three dimensions. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Comparing the effect of topical application of human milk and dry cord care on umbilical cord separation time in healthy newborn infants.

PubMed

Aghamohammadi, Azar; Zafari, Mandana; Moslemi, Leila

2012-06-01

Comparing the effect of topical human milk application and dry cord care on cord separation time. This research was a randomized clinical trial study on 130 singleton and mature newborns. Newborns were placed randomly in groups of topical application of human milk and dry cord care. The umbilical separation time was compared in the two groups. Data was analyzed by SPSS software. Independent Samples t-Test, χ(2), Fisher were used in this study. Median time of cord separation in human milk application group (150.95±28.68 hours) was significantly shorter than dry cord care group (180.93±37.42 hours) (P<0.001). Topical application of human milk on the remaining part of the cord reduces the cord separation time and it can be used as an easy, cheap and non invasive way for cord care.

Cytotoxic and multidrug resistance reversal activity of a vegetable, 'Anastasia Red', a variety of sweet pepper.

PubMed

Motohashi, Noboru; Wakabayashi, Hidetsugu; Kurihara, Teruo; Takada, Yuko; Maruyama, Shichiro; Sakagami, Hiroshi; Nakashima, Hideki; Tani, Satoru; Shirataki, Yoshiaki; Kawase, Masami; Wolfard, Kristina; Molnár, Joseph

2003-04-01

The vegetable, Anastasia Red, Capsicum annuum L. var. angulosum Mill. (Solanaceae) was successively extracted with hexane, acetone, methanol and 70% methanol, and the extracts were further separated into a total of 21 fractions by silica gel or octadecylsilane (ODS) column chromatography. The biological activities of extracts and fractions were determined. These extracts showed relatively higher cytotoxic activity against two human oral tumor cell lines (HSC-2, HSG) than against normal human gingival fibroblasts (HGF), suggesting a tumor-specific cytotoxic activity. The cytotoxic activity of these extracts was enhanced by fractionation on silica gel [H2, A2, M1-M3] or ODS column chromatography [70M]. Several fractions [H2, H4, H5, A1, A2, A3, A5, A6, A7, M2] reversed the multidrug resistance (MDR) phenotype with L5178 mouse lymphoma T cells, more efficiently than (+/-)-verapamil. The extracts and fractions did not show any detectable anti-human immunodeficiency virus (HIV) or anti-Helicobacter pylori activity. Thus, this study suggests the effective and selective antitumor potential of 'Anastasia Red' of sweet pepper for further phytochemical and biological investigation. Copyright 2003 John Wiley & Sons, Ltd.

Human tRNA genes function as chromatin insulators

PubMed Central

Raab, Jesse R; Chiu, Jonathan; Zhu, Jingchun; Katzman, Sol; Kurukuti, Sreenivasulu; Wade, Paul A; Haussler, David; Kamakaka, Rohinton T

2012-01-01

Insulators help separate active chromatin domains from silenced ones. In yeast, gene promoters act as insulators to block the spread of Sir and HP1 mediated silencing while in metazoans most insulators are multipartite autonomous entities. tDNAs are repetitive sequences dispersed throughout the human genome and we now show that some of these tDNAs can function as insulators in human cells. Using computational methods, we identified putative human tDNA insulators. Using silencer blocking, transgene protection and repressor blocking assays we show that some of these tDNA-containing fragments can function as barrier insulators in human cells. We find that these elements also have the ability to block enhancers from activating RNA pol II transcribed promoters. Characterization of a putative tDNA insulator in human cells reveals that the site possesses chromatin signatures similar to those observed at other better-characterized eukaryotic insulators. Enhanced 4C analysis demonstrates that the tDNA insulator makes long-range chromatin contacts with other tDNAs and ETC sites but not with intervening or flanking RNA pol II transcribed genes. PMID:22085927

Effects of fenspiride on human bronchial cyclic nucleotide phosphodiesterase isoenzymes: functional and biochemical study.

PubMed

Cortijo, J; Naline, E; Ortiz, J L; Berto, L; Girard, V; Malbezin, M; Advenier, C; Morcillo, E J

1998-01-02

We have investigated the role of human bronchial cyclic nucleotide phosphodiesterases in the effects of fenspiride, a drug endowed with bronchodilator and anti-inflammatory properties. Functional studies on human isolated bronchi showed that fenspiride (10(-6)-3 x 10(-3) M, 30 min) induced a shift to the left of the concentration-response curves for isoprenaline and sodium nitroprusside with -logEC50 values of 4.1+/-0.1 (n = 7) and 3.5+/-0.2 (n = 8), respectively. Biochemical studies were carried out on three human bronchi in which separation of cyclic nucleotide phosphodiesterase isoenzymes was performed by ion exchange chromatography followed by determination of phosphodiesterase activity with a radioisotopic method. Phosphodiesterase 4 (cyclic AMP-specific) and phosphodiesterase 5 (cyclic GMP-specific) were the major phosphodiesterase isoforms present in the human bronchial tissue. The presence of phosphodiesterase 1 (Ca2+/calmodulin-stimulated), phosphodiesterase 2 (cyclic GMP-stimulated) and, in two cases, phosphodiesterase 3 (cyclic GMP-inhibited) was also identified. Fenspiride inhibited phosphodiesterase 4 and phosphodiesterase 3 activities with -logIC50 values of 4.16+/-0.09 and 3.44+/-0.12, respectively. Phosphodiesterase 5 activity was also inhibited with a -logIC50 value of approximately 3.8. Fenspiride (< or = 10(-3) M) produced less than 25% inhibition of phosphodiesterase 1 and phosphodiesterase 2 activities. In conclusion, fenspiride is an effective inhibitor of both cyclic AMP and cyclic GMP hydrolytic activity in human bronchial tissues and this action may contribute to its airway effects.

Coil planet centrifugation as a means for small particle separation

NASA Technical Reports Server (NTRS)

Herrmann, F. T.

1983-01-01

The coil planet centrifuge uses a centrifugal force field to provide separation of particles based on differences in sedimentation rates by flow through a rotating coiled tube. Three main separations are considered: (1) single phase fresh sheep and human erythrocytes, (2) single phase fixed heep and human erythrocytes, and (3) electrophoretically enhanced single phase fresh sheep and human erythrocytes.

Structure and substrate recruitment of the human spindle checkpoint kinase Bub1.

PubMed

Kang, Jungseog; Yang, Maojun; Li, Bing; Qi, Wei; Zhang, Chao; Shokat, Kevan M; Tomchick, Diana R; Machius, Mischa; Yu, Hongtao

2008-11-07

In mitosis, the spindle checkpoint detects a single unattached kinetochore, inhibits the anaphase-promoting complex or cyclosome (APC/C), and prevents premature sister chromatid separation. The checkpoint kinase Bub1 contributes to checkpoint sensitivity through phosphorylating the APC/C activator, Cdc20, and inhibiting APC/C catalytically. We report here the crystal structure of the kinase domain of Bub1, revealing the requirement of an N-terminal extension for its kinase activity. Though the activation segment of Bub1 is ordered and has structural features indicative of active kinases, the C-terminal portion of this segment sterically restricts substrate access to the active site. Bub1 uses docking motifs, so-called KEN boxes, outside its kinase domain to recruit Cdc20, one of two known KEN box receptors. The KEN boxes of Bub1 are required for the spindle checkpoint in human cells. Therefore, its unusual active-site conformation and mode of substrate recruitment suggest that Bub1 has an exquisitely tuned specificity for Cdc20.

Effect of anti-GM2 antibodies on rat sciatic nerve: electrophysiological and morphological study.

PubMed

Ortiz, Nicolau; Sabaté, M Mar; Garcia, Neus; Santafe, Manel M; Lanuza, M Angel; Tomàs, Marta; Tomàs, Josep

2009-03-31

We found that a monoclonal human IgM anti-GM2 was fixed in rat sciatic axons and Schwann cells and was able to activate human complement. The passive transfer of IgM and complement in sciatic nerves can induce an acute alteration in nerve conduction. When the transfer of IgM plus complement was repeated for 10 days, the compound action motor potential amplitude was very low and the morphological study showed axons and myelin damage. Without human complement, IgM can only slightly disorganize the myelin by separating some layers, probably by interfering with the functional role of gangliosides in the myelin package.

Featured Article: Isolation, characterization, and cultivation of human hepatocytes and non-parenchymal liver cells

PubMed Central

Pfeiffer, Elisa; Kegel, Victoria; Zeilinger, Katrin; Hengstler, Jan G; Nüssler, Andreas K; Seehofer, Daniel

2015-01-01

Primary human hepatocytes (PHH) are considered to be the gold standard for in vitro testing of xenobiotic metabolism and hepatotoxicity. However, PHH cultivation in 2D mono-cultures leads to dedifferentiation and a loss of function. It is well known that hepatic non-parenchymal cells (NPC), such as Kupffer cells (KC), liver endothelial cells (LEC), and hepatic stellate cells (HSC), play a central role in the maintenance of PHH functions. The aims of the present study were to establish a protocol for the simultaneous isolation of human PHH and NPC from the same tissue specimen and to test their suitability for in vitro co-culture. Human PHH and NPC were isolated from tissue obtained by partial liver resection by a two-step EDTA/collagenase perfusion technique. The obtained cell fractions were purified by Percoll density gradient centrifugation. KC, LEC, and HSC contained in the NPC fraction were separated using specific adherence properties and magnetic activated cell sorting (MACS®). Identified NPC revealed a yield of 1.9 × 106 KC, 2.7 × 105 LEC and 4.7 × 105 HSC per gram liver tissue, showing viabilities >90%. Characterization of these NPC showed that all populations went through an activation process, which influenced the cell fate. The activation of KC strongly depended on the tissue quality and donor anamnesis. KC became activated in culture in association with a loss of viability within 4–5 days. LEC lost specific features during culture, while HSC went through a transformation process into myofibroblasts. The testing of different culture conditions for HSC demonstrated that they can attenuate, but not prevent dedifferentiation in vitro. In conclusion, the method described allows the isolation and separation of PHH and NPC in high quality and quantity from the same donor. PMID:25394621

Acoustofluidic bacteria separation

NASA Astrophysics Data System (ADS)

Li, Sixing; Ma, Fen; Bachman, Hunter; Cameron, Craig E.; Zeng, Xiangqun; Huang, Tony Jun

2017-01-01

Bacterial separation from human blood samples can help with the identification of pathogenic bacteria for sepsis diagnosis. In this work, we report an acoustofluidic device for label-free bacterial separation from human blood samples. In particular, we exploit the acoustic radiation force generated from a tilted-angle standing surface acoustic wave (taSSAW) field to separate Escherichia coli from human blood cells based on their size difference. Flow cytometry analysis of the E. coli separated from red blood cells shows a purity of more than 96%. Moreover, the label-free electrochemical detection of the separated E. coli displays reduced non-specific signals due to the removal of blood cells. Our acoustofluidic bacterial separation platform has advantages such as label-free separation, high biocompatibility, flexibility, low cost, miniaturization, automation, and ease of in-line integration. The platform can be incorporated with an on-chip sensor to realize a point-of-care sepsis diagnostic device.

A human lung mast cell chymotrypsin-like enzyme. Identification and partial characterization.

PubMed

Wintroub, B U; Kaempfer, C E; Schechter, N M; Proud, D

1986-01-01

We have used a high performance liquid chromatography assay, which detects chymotryptic cleavage of the phe8-his9 bond of angiotensin I to yield angiotensin II, in order to examine human lung mast cells for the presence of chymotryptic activity. Mast cells, purified from human lung by enzymatic dispersion, countercurrent elutriation, and Percoll gradient centrifugation, were lysed or challenged with goat anti-human IgE. In multiple experiments angiotensin II-converting activity was detected in lysates of 10-99% pure mast cell preparations. Regression analysis of net percent release values of histamine and the angiotensin I-converting activity from dose-response experiments demonstrated a correlation between the two parameters, indicating that the chymotrypsin-like enzyme is a constituent of the mast cell secretory granule. The chymotryptic activity was completely inhibited by 10(-3) M phenylmethylsulfonylfluoride but not by 10(-3) M Captopril, and the pH optimum of activity was 7.5-9.5. Gel filtration of released material separated the activity from tryptase and demonstrated an approximate molecular weight of 30-35,000. The mast cell enzyme, like a human skin chymotrypsin-like proteinase, can be distinguished from leukocyte cathepsin G by lack of susceptibility to inhibition by bovine pancreatic trypsin inhibitor. Thus, an enzyme with limited chymotryptic specificity is present in human lung mast cells. The Michaelis constant of the enzyme for angiotensin I of 6.0 X 10(-5) M is similar to that of endothelial cell angiotensin-converting enzyme and is consistent with a reaction of physiologic importance.

Selective Suppression of Endothelial Cell Apoptosis by the High Molecular Weight Form of Adiponectin

PubMed Central

Kobayashi, Hideki; Ouchi, Noriyuki; Kihara, Shinji; Walsh, Kenneth; Kumada, Masahiro; Abe, Yuki; Funahashi, Tohru; Matsuzawa, Yuji

2015-01-01

Adiponectin is an adipocyte-derived, antiatherogenic protein that is present in serum as three isoforms. Total adiponectin levels are decreased in obese or diabetic humans or animal models. This study was designed to elucidate the relative isoform distribution of adiponectin in human disease states and identify the active form of adiponectin toward vascular endothelial cells. The percentage of high molecular weight form (HMW) per total adiponectin was significantly lower in patients with coronary artery disease than control subjects, whereas the hexamer form was similar and the trimer form was significantly higher. During weight reduction in obese subjects, the HMW form increased and the trimer and hexamer forms decreased. Recombinant adiponectin dose-dependently suppressed apoptosis and caspase-3 activity in human umbilical vein endothelial cells (HUVECs). Transduction with dominant-negative AMP-activated protein kinase (AMPK) abolished the suppressive effect of adiponectin on HUVECs. Gel filtration chromatography was used to separate the adiponectin isoforms, and the antiapoptotic effect toward HUVECs was only observed with the HMW form. These data suggest that HMW adiponectin specifically confers the vascular-protective activities of this adipocytokine. PMID:14752031

An evolutionary perspective on human physical activity: implications for health.

PubMed

Eaton, S Boyd; Eaton, Stanley B

2003-09-01

At present, human genes and human lives are incongruent, especially in affluent Western nations. When our current genome was originally selected, daily physical exertion was obligatory; our biochemistry and physiology are designed to function optimally in such circumstances. However, today's mechanized, technologically oriented conditions allow and even promote an unprecedentedly sedentary lifestyle. Many important health problems are affected by this imbalance, including atherosclerosis, obesity, age-related fractures and diabetes, among others. Most physicians recognize that regular exercise is a critical component of effective health promotion regimens, but there is substantial disagreement about details, most importantly volume: how much daily caloric expenditure, as physical activity, is desirable. Because epidemiology-based recommendations vary, often confusing and alienating the health-conscious public, an independent estimate, arising from a separate scientific discipline, is desirable, at least for purposes of triangulation. The retrojected level of ancestral physical activity might meet this need. The best available such reconstruction suggests that the World Health Organization's recommendation, a physical activity level of 1.75 ( approximately 2.1 MJ (490 kcal)/d), most closely approximates the Paleolithic standard, that for which our genetic makeup was originally selected.

Reward-Guided Learning with and without Causal Attribution

PubMed Central

Jocham, Gerhard; Brodersen, Kay H.; Constantinescu, Alexandra O.; Kahn, Martin C.; Ianni, Angela M.; Walton, Mark E.; Rushworth, Matthew F.S.; Behrens, Timothy E.J.

2016-01-01

Summary When an organism receives a reward, it is crucial to know which of many candidate actions caused this reward. However, recent work suggests that learning is possible even when this most fundamental assumption is not met. We used novel reward-guided learning paradigms in two fMRI studies to show that humans deploy separable learning mechanisms that operate in parallel. While behavior was dominated by precise contingent learning, it also revealed hallmarks of noncontingent learning strategies. These learning mechanisms were separable behaviorally and neurally. Lateral orbitofrontal cortex supported contingent learning and reflected contingencies between outcomes and their causal choices. Amygdala responses around reward times related to statistical patterns of learning. Time-based heuristic mechanisms were related to activity in sensorimotor corticostriatal circuitry. Our data point to the existence of several learning mechanisms in the human brain, of which only one relies on applying known rules about the causal structure of the task. PMID:26971947

Promoter selection in human mitochondria involves binding of a transcription factor to orientation-independent upstream regulatory elements.

PubMed

Fisher, R P; Topper, J N; Clayton, D A

1987-07-17

Selective transcription of human mitochondrial DNA requires a transcription factor (mtTF) in addition to an essentially nonselective RNA polymerase. Partially purified mtTF is able to sequester promoter-containing DNA in preinitiation complexes in the absence of mitochondrial RNA polymerase, suggesting a DNA-binding mechanism for factor activity. Functional domains, required for positive transcriptional regulation by mtTF, are identified within both major promoters of human mtDNA through transcription of mutant promoter templates in a reconstituted in vitro system. These domains are essentially coextensive with DNA sequences protected from nuclease digestion by mtTF-binding. Comparison of the sequences of the two mtTF-responsive elements reveals significant homology only when one sequence is inverted; the binding sites are in opposite orientations with respect to the predominant direction of transcription. Thus mtTF may function bidirectionally, requiring additional protein-DNA interactions to dictate transcriptional polarity. The mtTF-responsive elements are arrayed as direct repeats, separated by approximately 80 bp within the displacement-loop region of human mitochondrial DNA; this arrangement may reflect duplication of an ancestral bidirectional promoter, giving rise to separate, unidirectional promoters for each strand.

Dosimetry of {sup 210}Po in humans, caribou, and wolves in northern Canada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, P.A.

1994-06-01

Effective doses from {sup 210}Po intake with caribou meat were determined for human residents in Baker Lake and Snowdrift in the Northwest Territories of Canada and compared to doses calculated from reported {sup 210}Po tissue activities in Alaskan and British residents. Effective doses were calculated to separate body tissues, using ICRP 60 human weighting factors and the ICRP 30 metabolic model for {sup 210}Po. Baker Lake and Alaskan effective doses were similar at 0.4 mSv y{sup {minus}1} and slightly higher than Snowdrift doses (0.3 mSv y{sup {minus}1}). Alaskan tissue activities indicated higher effective doses to liver, bone surfaces and redmore » marrow and lower doses to spleen than the {sup 210}Po metabolic model (ICRP 1979a) predicts. Effective doses to Baker Lake and Snowdrift caribou and wolves, calculated from tissue activities, ranged from 7-20 mSv y{sup {minus}1} using human weighting factors for comparison to human doses only. Effective doses to northern Canadians and wildlife were, respectively, 7-11% and 1.8-5 times an estimated human background of 4 mSv y{sup {minus}} from all sources. 51 refs., 2 figs., 9 tabs.« less

Adipogenesis-related increase of semicarbazide-sensitive amine oxidase and monoamine oxidase in human adipocytes.

PubMed

Bour, Sandy; Daviaud, Danièle; Gres, Sandra; Lefort, Corinne; Prévot, Danielle; Zorzano, Antonio; Wabitsch, Martin; Saulnier-Blache, Jean-Sébastien; Valet, Philippe; Carpéné, Christian

2007-08-01

A strong induction of semicarbazide-sensitive amine oxidase (SSAO) has previously been reported during murine preadipocyte lineage differentiation but it remains unknown whether this emergence also occurs during adipogenesis in man. Our aim was to compare SSAO and monoamine oxidase (MAO) expression during in vitro differentiation of human preadipocytes and in adipose and stroma-vascular fractions of human fat depots. A human preadipocyte cell strain from a patient with Simpson-Golabi-Behmel syndrome was first used to follow amine oxidase expression during in vitro differentiation. Then, human preadipocytes isolated from subcutaneous adipose tissues were cultured under conditions promoting ex vivo adipose differentiation and tested for MAO and SSAO expression. Lastly, human adipose tissue was separated into mature adipocyte and stroma-vascular fractions for analyses of MAO and SSAO at mRNA, protein and activity levels. Both SSAO and MAO were increased from undifferentiated preadipocytes to lipid-laden cells in all the models: 3T3-F442A and 3T3-L1 murine lineages, human SGBS cell strain or human preadipocytes in primary culture. In human subcutaneous adipose tissue, the adipocyte-enriched fraction exhibited seven-fold higher amine oxidase activity and contained three- to seven-fold higher levels of mRNAs encoded by MAO-A, MAO-B, AOC3 and AOC2 genes than the stroma-vascular fraction. MAO-A and AOC3 genes accounted for the majority of their respective MAO and SSAO activities in human adipose tissue. Most of the SSAO and MAO found in adipose tissue originated from mature adipocytes. Although the mechanism and role of adipogenesis-related increase in amine oxidase expression remain to be established, the resulting elevated levels of amine oxidase activities found in human adipocytes may be of potential interest for therapeutic intervention in obesity.

Effect of local and global geomagnetic activity on human cardiovascular homeostasis.

PubMed

Dimitrova, Svetla; Stoilova, Irina; Yanev, Toni; Cholakov, Ilia

2004-02-01

The authors investigated the effects of local and planetary geomagnetic activity on human physiology. They collected data in Sofia, Bulgaria, from a group of 86 volunteers during the periods of the autumnal and vernal equinoxes. They used the factors local/planetary geomagnetic activity, day of measurement, gender, and medication use to apply a four-factor multiple analysis of variance. They also used a post hoc analysis to establish the statistical significance of the differences between the average values of the measured physiological parameters in the separate factor levels. In addition, the authors performed correlation analysis between the physiological parameters examined and geophysical factors. The results revealed that geomagnetic changes had a statistically significant influence on arterial blood pressure. Participants expressed this reaction with weak local geomagnetic changes and when major and severe global geomagnetic storms took place.

Separation of replication and transcription domains in nucleoli.

PubMed

Smirnov, E; Borkovec, J; Kováčik, L; Svidenská, S; Schröfel, A; Skalníková, M; Švindrych, Z; Křížek, P; Ovesný, M; Hagen, G M; Juda, P; Michalová, K; Cardoso, M C; Cmarko, D; Raška, I

2014-12-01

In mammalian cells, active ribosomal genes produce the 18S, 5.8S and 28S RNAs of ribosomal particles. Transcription levels of these genes are very high throughout interphase, and the cell needs a special strategy to avoid collision of the DNA polymerase and RNA polymerase machineries. To investigate this problem, we measured the correlation of various replication and transcription signals in the nucleoli of HeLa, HT-1080 and NIH 3T3 cells using a specially devised software for analysis of confocal images. Additionally, to follow the relationship between nucleolar replication and transcription in living cells, we produced a stable cell line expressing GFP-RPA43 (subunit of RNA polymerase I, pol I) and RFP-PCNA (the sliding clamp protein) based on human fibrosarcoma HT-1080 cells. We found that replication and transcription signals are more efficiently separated in nucleoli than in the nucleoplasm. In the course of S phase, separation of PCNA and pol I signals gradually increased. During the same period, separation of pol I and incorporated Cy5-dUTP signals decreased. Analysis of single molecule localization microscopy (SMLM) images indicated that transcriptionally active FC/DFC units (i.e. fibrillar centers with adjacent dense fibrillar components) did not incorporate DNA nucleotides. Taken together, our data show that replication of the ribosomal genes is spatially separated from their transcription, and FC/DFC units may provide a structural basis for that separation. Copyright © 2014 Elsevier Inc. All rights reserved.

AMP-activated kinase in human spermatozoa: identification, intracellular localization, and key function in the regulation of sperm motility.

PubMed

Calle-Guisado, Violeta; de Llera, Ana Hurtado; Martin-Hidalgo, David; Mijares, Jose; Gil, Maria C; Alvarez, Ignacio S; Bragado, Maria J; Garcia-Marin, Luis J

2017-01-01

AMP-activated kinase (AMPK), a protein that regulates energy balance and metabolism, has recently been identified in boar spermatozoa where regulates key functional sperm processes essential for fertilization. This work's aims are AMPK identification, intracellular localization, and their role in human spermatozoa function. Semen was obtained from healthy human donors. Sperm AMPK and phospho-Thr172-AMPK were analyzed by Western blotting and indirect immunofluorescence. High- and low-quality sperm populations were separated by a 40%-80% density gradient. Human spermatozoa motility was evaluated by an Integrated Semen Analysis System (ISAS) in the presence or absence of the AMPK inhibitor compound C (CC). AMPK is localized along the human spermatozoa, at the entire acrosome, midpiece and tail with variable intensity, whereas its active form, phospho-Thr172-AMPK, shows a prominent staining at the acrosome and sperm tail with a weaker staining in the midpiece and the postacrosomal region. Interestingly, spermatozoa bearing an excess residual cytoplasm show strong AMPK staining in this subcellular compartment. Both AMPK and phospho-Thr172-AMPK human spermatozoa contents exhibit important individual variations. Moreover, active AMPK is predominant in the high motility sperm population, where shows a stronger intensity compared with the low motility sperm population. Inhibition of AMPK activity in human spermatozoa by CC treatment leads to a significant reduction in any sperm motility parameter analyzed: percent of motile sperm, sperm velocities, progressivity, and other motility coefficients. This work identifies and points out AMPK as a new molecular mechanism involved in human spermatozoa motility. Further AMPK implications in the clinical efficiency of assisted reproduction and in other reproductive areas need to be studied.

AMP-activated kinase in human spermatozoa: identification, intracellular localization, and key function in the regulation of sperm motility

PubMed Central

Calle-Guisado, Violeta; de Llera, Ana Hurtado; Martin-Hidalgo, David; Mijares, Jose; Gil, Maria C; Alvarez, Ignacio S; Bragado, Maria J; Garcia-Marin, Luis J

2017-01-01

AMP-activated kinase (AMPK), a protein that regulates energy balance and metabolism, has recently been identified in boar spermatozoa where regulates key functional sperm processes essential for fertilization. This work's aims are AMPK identification, intracellular localization, and their role in human spermatozoa function. Semen was obtained from healthy human donors. Sperm AMPK and phospho-Thr172-AMPK were analyzed by Western blotting and indirect immunofluorescence. High- and low-quality sperm populations were separated by a 40%–80% density gradient. Human spermatozoa motility was evaluated by an Integrated Semen Analysis System (ISAS) in the presence or absence of the AMPK inhibitor compound C (CC). AMPK is localized along the human spermatozoa, at the entire acrosome, midpiece and tail with variable intensity, whereas its active form, phospho-Thr172-AMPK, shows a prominent staining at the acrosome and sperm tail with a weaker staining in the midpiece and the postacrosomal region. Interestingly, spermatozoa bearing an excess residual cytoplasm show strong AMPK staining in this subcellular compartment. Both AMPK and phospho-Thr172-AMPK human spermatozoa contents exhibit important individual variations. Moreover, active AMPK is predominant in the high motility sperm population, where shows a stronger intensity compared with the low motility sperm population. Inhibition of AMPK activity in human spermatozoa by CC treatment leads to a significant reduction in any sperm motility parameter analyzed: percent of motile sperm, sperm velocities, progressivity, and other motility coefficients. This work identifies and points out AMPK as a new molecular mechanism involved in human spermatozoa motility. Further AMPK implications in the clinical efficiency of assisted reproduction and in other reproductive areas need to be studied. PMID:27678462

Functional organization of human intraparietal and frontal cortex for attending, looking, and pointing

NASA Technical Reports Server (NTRS)

Astafiev, Serguei V.; Shulman, Gordon L.; Stanley, Christine M.; Snyder, Abraham Z.; Van Essen, David C.; Corbetta, Maurizio

2003-01-01

We studied the functional organization of human posterior parietal and frontal cortex using functional magnetic resonance imaging (fMRI) to map preparatory signals for attending, looking, and pointing to a peripheral visual location. The human frontal eye field and two separate regions in the intraparietal sulcus were similarly recruited in all conditions, suggesting an attentional role that generalizes across response effectors. However, the preparation of a pointing movement selectively activated a different group of regions, suggesting a stronger role in motor planning. These regions were lateralized to the left hemisphere, activated by preparation of movements of either hand, and included the inferior and superior parietal lobule, precuneus, and posterior superior temporal sulcus, plus the dorsal premotor and anterior cingulate cortex anteriorly. Surface-based registration of macaque cortical areas onto the map of fMRI responses suggests a relatively good spatial correspondence between human and macaque parietal areas. In contrast, large interspecies differences were noted in the topography of frontal areas.

Verification of the effects of Schumann frequency range electromagnetic fields on the human cardiovascular system

NASA Astrophysics Data System (ADS)

Tuzhilkin, D. A.; Borodin, A. S.

2017-11-01

The results of the study of variations in the electromagnetic background parameters of the Schumann resonator frequency range and the variability indices of the human heart period during its free activity are presented on the basis of 24-hour synchronous monitoring data. It is shown that the integral evaluation of the conjugacy of the heart rate variability indices from the Schumann resonance parameters is extremely weak. In this case, the differential evaluation of this dependence with separation into characteristic time intervals of the day, characterized by different motor activity of the subjects, becomes significantly higher. The number of volunteers whose conjugacy is characterized by a strong correlation in some cases reaches 35 percent of the sample.

Supermacroporous cryogel matrix for integrated protein isolation. Immobilized metal affinity chromatographic purification of urokinase from cell culture broth of a human kidney cell line.

PubMed

Kumar, Ashok; Bansal, Vibha; Andersson, Jonatan; Roychoudhury, Pradip K; Mattiasson, Bo

2006-01-20

A new type of supermacroporous, monolithic, cryogel affinity adsorbent was developed, allowing the specific capture of urokinase from conditioned media of human fibrosarcoma cell line HT1080. The affinity adsorbent was designed with the objective of using it as a capture column in an integrated perfusion/protein separation bioreactor setup. A comparative study between the utility of this novel cryogel based matrix and the conventional Sepharose based affinity matrix for the continuous capture of urokinase in an integrated bioreactor system was performed. Cu(II)-ion was coupled to epoxy activated polyacrylamide cryogel and Sepharose using iminodiacetic acid (IDA) as the chelating ligand. About 27-fold purification of urokinase from the conditioned culture media was achieved with Cu(II)-IDA-polyacrylamide cryogel column giving specific activity of about 814 Plough units (PU)/mg protein and enzyme yields of about 80%. High yields (95%) were obtained with Cu(II)-IDA-Sepharose column by virtue of its high binding capacity. However, the adsorbent showed lower selectivity as compared to cryogel matrix giving specific activity of 161 PU/mg protein and purification factor of 5.3. The high porosity, selectivity and reasonably good binding capacity of Cu(II)-IDA-polyacrylamide cryogel column make it a promising option for use as a protein capture column in integrated perfusion/separation processes. The urokinase peak pool from Cu(II)-IDA-polyacrylamide cryogel column could be further resolved into separate fractions for high and low molecular weight forms of urokinase by gel filtration chromatography on Sephacryl S-200. The selectivity of the cryogel based IMAC matrix for urokinase was found to be higher as compared to that of Cu(II)-IDA-Sepharose column.

Evaluation of somatosensory cortical differences between flutter and vibration tactile stimuli.

PubMed

Han, Sang Woo; Chung, Yoon Gi; Kim, Hyung-Sik; Chung, Soon-Cheol; Park, Jang-Yeon; Kim, Sung-Phil

2013-01-01

In parallel with advances in haptic-based mobile computing systems, understanding of the neural processing of vibrotactile information becomes of great importance. In the human nervous system, two types of vibrotactile information, flutter and vibration, are delivered from mechanoreceptors to the somatosensory cortex through segregated neural afferents. To investigate how the somatosensory cortex differentiates flutter and vibration, we analyzed the cortical responses to vibrotactile stimuli with a wide range of frequencies. Specifically, we examined whether cortical activity changed most around 50 Hz, which is known as a boundary between flutter and vibration. We explored various measures to evaluate separability of cortical activity across frequency and found that the hypothesis margin method resulted in the greatest separability between flutter and vibration. This result suggests that flutter and vibration information may be processed by different neural processes in the somatosensory cortex.

Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds.

PubMed

Delfosse, Vanessa; Dendele, Béatrice; Huet, Tiphaine; Grimaldi, Marina; Boulahtouf, Abdelhay; Gerbal-Chaloin, Sabine; Beucher, Bertrand; Roecklin, Dominique; Muller, Christina; Rahmani, Roger; Cavaillès, Vincent; Daujat-Chavanieu, Martine; Vivat, Valérie; Pascussi, Jean-Marc; Balaguer, Patrick; Bourguet, William

2015-09-03

Humans are chronically exposed to multiple exogenous substances, including environmental pollutants, drugs and dietary components. Many of these compounds are suspected to impact human health, and their combination in complex mixtures could exacerbate their harmful effects. Here we demonstrate that a pharmaceutical oestrogen and a persistent organochlorine pesticide, both exhibiting low efficacy when studied separately, cooperatively bind to the pregnane X receptor, leading to synergistic activation. Biophysical analysis shows that each ligand enhances the binding affinity of the other, so the binary mixture induces a substantial biological response at doses at which each chemical individually is inactive. High-resolution crystal structures reveal the structural basis for the observed cooperativity. Our results suggest that the formation of 'supramolecular ligands' within the ligand-binding pocket of nuclear receptors contributes to the synergistic toxic effect of chemical mixtures, which may have broad implications for the fields of endocrine disruption, toxicology and chemical risk assessment.

Separate encoding of model-based and model-free valuations in the human brain.

PubMed

Beierholm, Ulrik R; Anen, Cedric; Quartz, Steven; Bossaerts, Peter

2011-10-01

Behavioral studies have long shown that humans solve problems in two ways, one intuitive and fast (System 1, model-free), and the other reflective and slow (System 2, model-based). The neurobiological basis of dual process problem solving remains unknown due to challenges of separating activation in concurrent systems. We present a novel neuroeconomic task that predicts distinct subjective valuation and updating signals corresponding to these two systems. We found two concurrent value signals in human prefrontal cortex: a System 1 model-free reinforcement signal and a System 2 model-based Bayesian signal. We also found a System 1 updating signal in striatal areas and a System 2 updating signal in lateral prefrontal cortex. Further, signals in prefrontal cortex preceded choices that are optimal according to either updating principle, while signals in anterior cingulate cortex and globus pallidus preceded deviations from optimal choice for reinforcement learning. These deviations tended to occur when uncertainty regarding optimal values was highest, suggesting that disagreement between dual systems is mediated by uncertainty rather than conflict, confirming recent theoretical proposals. Copyright © 2011 Elsevier Inc. All rights reserved.

Contribution of human and climate change impacts to changes in streamflow of Canada.

PubMed

Tan, Xuezhi; Gan, Thian Yew

2015-12-04

Climate change exerts great influence on streamflow by changing precipitation, temperature, snowpack and potential evapotranspiration (PET), while human activities in a watershed can directly alter the runoff production and indirectly through affecting climatic variables. However, to separate contribution of anthropogenic and natural drivers to observed changes in streamflow is non-trivial. Here we estimated the direct influence of human activities and climate change effect to changes of the mean annual streamflow (MAS) of 96 Canadian watersheds based on the elasticity of streamflow in relation to precipitation, PET and human impacts such as land use and cover change. Elasticities of streamflow for each watershed are analytically derived using the Budyko Framework. We found that climate change generally caused an increase in MAS, while human impacts generally a decrease in MAS and such impact tends to become more severe with time, even though there are exceptions. Higher proportions of human contribution, compared to that of climate change contribution, resulted in generally decreased streamflow of Canada observed in recent decades. Furthermore, if without contributions from retreating glaciers to streamflow, human impact would have resulted in a more severe decrease in Canadian streamflow.

The sweet taste quality is linked to a cluster of taste fibers in primates: lactisole diminishes preference and responses to sweet in S fibers (sweet best) chorda tympani fibers of M. fascicularis monkey.

PubMed

Wang, Yiwen; Danilova, Vicktoria; Cragin, Tiffany; Roberts, Thomas W; Koposov, Alexey; Hellekant, Göran

2009-02-18

Psychophysically, sweet and bitter have long been considered separate taste qualities, evident already to the newborn human. The identification of different receptors for sweet and bitter located on separate cells of the taste buds substantiated this separation. However, this finding leads to the next question: is bitter and sweet also kept separated in the next link from the taste buds, the fibers of the taste nerves? Previous studies in non-human primates, P. troglodytes, C. aethiops, M. mulatta, M. fascicularis and C. jacchus, suggest that the sweet and bitter taste qualities are linked to specific groups of fibers called S and Q fibers. In this study we apply a new sweet taste modifier, lactisole, commercially available as a suppressor of the sweetness of sugars on the human tongue, to test our hypothesis that sweet taste is conveyed in S fibers. We first ascertained that lactisole exerted similar suppression of sweetness in M. fascicularis, as reported in humans, by recording their preference of sweeteners and non- sweeteners with and without lactisole in two-bottle tests. The addition of lactisole significantly diminished the preference for all sweeteners but had no effect on the intake of non-sweet compounds or the intake of water. We then recorded the response to the same taste stimuli in 40 single chorda tympani nerve fibers. Comparison between single fiber nerve responses to stimuli with and without lactisole showed that lactisole only suppressed the responses to sweeteners in S fibers. It had no effect on the responses to any other stimuli in all other taste fibers. In M. fascicularis, lactisole diminishes the attractiveness of compounds, which taste sweet to humans. This behavior is linked to activity of fibers in the S-cluster. Assuming that lactisole blocks the T1R3 monomer of the sweet taste receptor T1R2/R3, these results present further support for the hypothesis that S fibers convey taste from T1R2/R3 receptors, while the impulse activity in non-S fibers originates from other kinds of receptors. The absence of the effect of lactisole on the faint responses in some S fibers to other stimuli as well as the responses to sweet and non-sweet stimuli in non-S fibers suggest that these responses originate from other taste receptors.

Science and technology integration for increased human potential and societal outcomes.

PubMed

Roco, Mihail C

2004-05-01

Unifying science based on the material unity of nature at the nanoscale provides a new foundation for knowledge, innovation, and integration of technology. Revolutionary and synergistic advances at the interfaces between previously separated fields of science, engineering and areas of relevance are ready to create nano-bio-info-cogno (NBIC) transforming tools. Developments in systems approach, mathematics, and computation in conjunction with NBIC allow us to understand the natural world and scientific research as closely coupled, complex, hierarchical entities. At this unique moment of scientific and technical achievement, improvement of human performance at individual and group levels, as well as development of suitable revolutionary products, becomes possible and these are primary goals for converging new technologies. NBIC addresses long-term advances in key areas of human activity, including working, learning, aging, group interaction, organizations, and human evolution ((Roco and Bainbridge, 2003)). Fundamentally new tools, technologies, and products will be integrated into individual and social human architecture. This introductory chapter of the Annals outlines research and education trends, funding activities, and the potential of development of revolutionary products and services.

Functional magnetic resonance imaging of the human spinal cord during vibration stimulation of different dermatomes.

PubMed

Lawrence, Jane M; Stroman, Patrick W; Kollias, Spyros S

2008-03-01

We investigated noninvasively areas of the healthy human spinal cord that become active in response to vibration stimulation of different dermatomes using functional magnetic resonance imaging (fMRI). The objectives of this study were to: (1) examine the patterns of consistent activity in the spinal cord during vibration stimulation of the skin, and (2) investigate the rostrocaudal distribution of active pixels when stimulation was applied to different dermatomes. FMRI of the cervical and lumbar spinal cord of seven healthy human subjects was carried out during vibration stimulation of six different dermatomes. In separate experiments, vibratory stimulation (about 50 Hz) was applied to the right biceps, wrist, palm, patella, Achilles tendon and left palm. The segmental distribution of activity observed by fMRI corresponded well with known spinal cord neuroanatomy. The peak number of active pixels was observed at the expected level of the spinal cord with some activity in the adjacent segments. The rostrocaudal distribution of activity was observed to correspond to the dermatome being stimulated. Cross-sectional localization of activity was primarily in dorsal areas but also spread into ventral and intermediate areas of the gray matter and a distinct laterality ipsilateral to the stimulated limb was not observed. We demonstrated that fMRI can detect a dermatome-dependent pattern of spinal cord activity during vibratory stimulation and can be used as a passive stimulus for the noninvasive assessment of the functional integrity of the human spinal cord. Demonstration of cross-sectional selectivity of the activation awaits further methodological and experimental refinements.

Blind source separation in retinal videos

NASA Astrophysics Data System (ADS)

Barriga, Eduardo S.; Truitt, Paul W.; Pattichis, Marios S.; Tüso, Dan; Kwon, Young H.; Kardon, Randy H.; Soliz, Peter

2003-05-01

An optical imaging device of retina function (OID-RF) has been developed to measure changes in blood oxygen saturation due to neural activity resulting from visual stimulation of the photoreceptors in the human retina. The video data that are collected represent a mixture of the functional signal in response to the retinal activation and other signals from undetermined physiological activity. Measured changes in reflectance in response to the visual stimulus are on the order of 0.1% to 1.0% of the total reflected intensity level which makes the functional signal difficult to detect by standard methods since it is masked by the other signals that are present. In this paper, we apply principal component analysis (PCA), blind source separation (BSS), using Extended Spatial Decorrelation (ESD) and independent component analysis (ICA) using the Fast-ICA algorithm to extract the functional signal from the retinal videos. The results revealed that the functional signal in a stimulated retina can be detected through the application of some of these techniques.

Cortical regions associated with orthostatic stress in conscious humans

NASA Astrophysics Data System (ADS)

Kimmerly, Derek S.; O'Leary, Debbie D.; Cechetto, Angela; Shoemaker, Kevin J.

2005-08-01

The purpose of this study was to determine the cortical structures associated with lower body negative pressure (LBNP)-induced baroreflex control using functional magnetic resonance imaging (fMRI). Heart rate (HR) and LBNP were simultaneously monitored during scanning. Central venous pressure (CVP), muscle sympathetic nerve activity (MSNA) and arterial blood pressure (ABP) were measured on a separate day. Random effects analyses (SPM2) were used to evaluate fMRI signal changes that correlated separately with both LBNP and HR (15 and 35-mmHg versus 5-mmHg LBNP). LBNP at 15- and 35-mmHg decreased CVP and increased MSNA, both P < 0.05 versus baseline) but only LBNP at 35- mmHg elevated HR. ABP was similar at all levels of LBNP . Cortical regions demonstrating increased activity at higher HR and greater LBNP included the right superior posterior insula and the cerebellum. Conversely, bilateral anterior insular cortices, the right anterior cingulate, amygdala, and mediodorsal nucleus of the thalamus showed decreased neural activation.

Human functional magnetic resonance imaging reveals separation and integration of shape and motion cues in biological motion processing.

PubMed

Jastorff, Jan; Orban, Guy A

2009-06-03

In a series of human functional magnetic resonance imaging experiments, we systematically manipulated point-light stimuli to identify the contributions of the various areas implicated in biological motion processing (for review, see Giese and Poggio, 2003). The first experiment consisted of a 2 x 2 factorial design with global shape and kinematics as factors. In two additional experiments, we investigated the contributions of local opponent motion, the complexity of the portrayed movement and a one-back task to the activation pattern. Experiment 1 revealed a clear separation between shape and motion processing, resulting in two branches of activation. A ventral region, extending from the lateral occipital sulcus to the posterior inferior temporal gyrus, showed a main effect of shape and its extension into the fusiform gyrus also an interaction. The dorsal region, including the posterior inferior temporal sulcus and the posterior superior temporal sulcus (pSTS), showed a main effect of kinematics together with an interaction. Region of interest analysis identified these interaction sites as the extrastriate and fusiform body areas (EBA and FBA). The local opponent motion cue yielded only little activation, limited to the ventral region (experiment 3). Our results suggest that the EBA and the FBA correspond to the initial stages in visual action analysis, in which the performed action is linked to the body of the actor. Moreover, experiment 2 indicates that the body areas are activated automatically even in the absence of a task, whereas other cortical areas like pSTS or frontal regions depend on the complexity of movements or task instructions for their activation.

Parahippocampal and retrosplenial contributions to human spatial navigation

PubMed Central

Epstein, Russell A.

2010-01-01

Spatial navigation is a core cognitive ability in humans and animals. Neuroimaging studies have identified two functionally-defined brain regions that activate during navigational tasks and also during passive viewing of navigationally-relevant stimuli such as environmental scenes: the parahippocampal place area (PPA) and the retrosplenial complex (RSC). Recent findings indicate that the PPA and RSC play distinct and complementary roles in spatial navigation, with the PPA more concerned with representation of the local visual scene and RSC more concerned with situating the scene within the broader spatial environment. These findings are a first step towards understanding the separate components of the cortical network that mediates spatial navigation in humans. PMID:18760955

Two distinct forms of Factor VIII coagulant protein in human plasma. Cleavage by thrombin, and differences in coagulant activity and association with von Willebrand factor.

PubMed Central

Weinstein, M J; Chute, L E

1984-01-01

We have characterized Factor VIII coagulant protein, present in normal human plasma, that reacts with a specific human 125I-labeled anti-human VIII:C antigen Fab antibody fragment. Two major Factor VIII coagulant antigen populations were present. The first, approximately 85% of the total antigen, was bound to von Willebrand factor and when tested in a standard one-stage assay had Factor VIII coagulant activity. The second antigenic population, eluting near fibrinogen when plasma was gel filtered, was not bound to von Willebrand protein, did not have Factor VIII coagulant activity unless activated, but did block anti-VIII:C Fab neutralization of clotting activity. The two antigenic populations were separable by cryoprecipitation and agarose gel electrophoresis. Although the two antigenic populations differed in their Factor VIII coagulant activity and in their binding to von Willebrand factor, the principal member of both populations is of mol wt 2.4 X 10(5). Both antigens, when proteolyzed by thrombin, were quickly converted to a 1 X 10(5)-mol wt form in association with the appearance of VIII:C activity. The 1 X 10(5)-mol wt antigen was further slowly degraded to an 8 X 10(4)-mol wt form while Factor VIII coagulant activity declined. These results demonstrate the presence of an inactive Factor VIII coagulant protein in plasma, not associated with von Willebrand factor, that can react with thrombin to yield Factor VIII coagulant activity. Images PMID:6421875

The relative role of climate change and human activities in the desertification process in Yulin region of northwest China.

PubMed

Wang, Tao; Sun, Jian-Guo; Han, Hui; Yan, Chang-Zhen

2012-12-01

To overcome the shortcoming of existing studies, this paper put forward a statistical vegetation-climate relationship model with integrated temporal and spatial characteristics. Based on this model, we quantitatively discriminated on the grid scale the relative role of climate change and human activities in the desertification dynamics from 1986 to 2000 in Yulin region. Yulin region's desertification development occurred mainly in the southern hilly and gully area and its reverse in the northwest sand and marsh area. This spatial pattern was especially evident and has never changed thoroughly. From the first time section (1986-1990) to the second (1991-1995), the desertification was developing as a whole, and either in the desertification development district or in the reverse district human activities' role was always occupying an overwhelmingly dominant position (they were 98.7% and 101.4%, respectively), the role of climate change was extremely slight. From the second time section (1991-1995) to the third (1996-2000), the desertification process was reaching a state of stability, in the desertification development district the role of climate change was nearly equivalent to that of human activities (they were 46.2% and 53.8% separately), and yet in the desertification reverse district, the role of human activities came up to 119.0%, the role of climate change amounted to -19.0%. In addition, the relative role of climate change and human activities possessed great spatial heterogeneity. The above conclusion rather coincides with the qualitative analysis in many literatures, which indicates that this method has certain rationality and can be utilized as a reference for the monitoring and studying of desertification in other areas.

A sensitive and specific radiochromatographic assay of fatty acid amide hydrolase activity.

PubMed

Maccarrone, M; Bari, M; Agrò, A F

1999-02-15

A radiochromatographic method has been set up in order to determine fatty acid amide hydrolase (FAAH) activity, based on reversed-phase high-performance liquid chromatography and on-line scintillation counting. The reaction products were separated using a C18 column eluted with methanol-water-acetic acid and quantitated with an external standard. Baseline separation of the acid product from the substrate was completed in less than 4 min, with a detection limit of 2.5 fmol arachidonic acid at a signal to noise ratio of 4:1. The method enabled to determine the kinetic constants (i.e., apparent Km of 2.0 +/- 0.2 microM and Vmax of 800 +/- 75 pmol. min-1. mg protein-1 toward anandamide) and the substrate specificity of human brain FAAH, as well as the extent of enzyme inhibition by some anandamide congeners. The femtomole sensitivity and the accuracy of the method allow detection and characterization of the activity of FAAH in very minute tissue samples or in samples where the enzymatic activity is very low. Copyright 1999 Academic Press.

Effects of three activities on annoyance responses to recorded flyovers. [human tolerance of jet aircraft noise

NASA Technical Reports Server (NTRS)

Gunn, W. J.; Shepherd, W. T.; Fletcher, J. L.

1975-01-01

Human subjects participated in an experiment in which they were engaged in TV viewing, telephone listening, or reverie (no activity) for a 1/2-hour session. During the session, they were exposed to a series of recorded aircraft sounds at the rate of one flight every 2 minutes. At each session, four levels of flyover noise, separated by 5 db increments were presented several times in a Latin Square balanced sequence. The peak levels of the noisiest flyover in any session was fixed at 95, 90, 85, 75, or 70 db. At the end of the test session, subjects recorded their responses to the aircraft sounds, using a bipolar scale which covered the range from very pleasant to extremely annoying. Responses to aircraft noises are found to be significantly affected by the particular activity in which the subjects are engaged.

Estimation of global anthropogenic dust aerosol using CALIOP satellite

NASA Astrophysics Data System (ADS)

Chen, B.; Huang, J.; Liu, J.

2014-12-01

Anthropogenic dust aerosols are those produced by human activity, which mainly come from cropland, pasture, and urban in this paper. Because understanding of the emissions of anthropogenic dust is still very limited, a new technique for separating anthropogenic dust from natural dustusing CALIPSO dust and planetary boundary layer height retrievalsalong with a land use dataset is introduced. Using this technique, the global distribution of dust is analyzed and the relative contribution of anthropogenic and natural dust sources to regional and global emissions are estimated. Local anthropogenic dust aerosol due to human activity, such as agriculture, industrial activity, transportation, and overgrazing, accounts for about 22.3% of the global continentaldust load. Of these anthropogenic dust aerosols, more than 52.5% come from semi-arid and semi-wet regions. On the whole, anthropogenic dust emissions from East China and India are higher than other regions.

Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors.

PubMed

Liu, Hesheng; Stufflebeam, Steven M; Sepulcre, Jorge; Hedden, Trey; Buckner, Randy L

2009-12-01

Cerebral lateralization is a fundamental property of the human brain and a marker of successful development. Here we provide evidence that multiple mechanisms control asymmetry for distinct brain systems. Using intrinsic activity to measure asymmetry in 300 adults, we mapped the most strongly lateralized brain regions. Both men and women showed strong asymmetries with a significant, but small, group difference. Factor analysis on the asymmetric regions revealed 4 separate factors that each accounted for significant variation across subjects. The factors were associated with brain systems involved in vision, internal thought (the default network), attention, and language. An independent sample of right- and left-handed individuals showed that hand dominance affects brain asymmetry but differentially across the 4 factors supporting their independence. These findings show the feasibility of measuring brain asymmetry using intrinsic activity fluctuations and suggest that multiple genetic or environmental mechanisms control cerebral lateralization.

Determination of active components of Ginkgo biloba in human urine by capillary high-performance liquid chromatography/mass spectrometry with on-line column-switching purification.

PubMed

Ding, Shujing; Dudley, Ed; Chen, Lijuan; Plummer, Sue; Tang, Jiandong; Newton, Russell P; Brenton, A Gareth

2006-01-01

Ginkgo biloba is one of the most popular herbal nutritional supplements, with terpene lactones and flavonoids being the two major active components. An on-line purification high-performance liquid chromatography/mass spectrometry (HPLC/MS) method was successfully developed for the quantitative determination of flavonoids and terpene lactones excreted in human urine after ingesting the herbal supplement. Satisfactory separation was obtained using a C18 capillary column made in-house with sample clean-up and pre-concentration achieved using a C18 pre-column with column switching. High selectivity and limits of detection of 1-18 ng/mL were achieved using a selected ion monitoring (SIM) scan in negative ion mode; the on-line solid-phase extraction (SPE) recovery of the active components in Ginkgo biloba determined in this study was greater than 75%. Copyright 2006 John Wiley & Sons, Ltd.

A facile method for emulsified oil-water separation by using polyethylenimine-coated magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Lü, Ting; Qi, Dongming; Zhang, Dong; Lü, Yulan; Zhao, Hongting

2018-04-01

Oil spills and oily wastewater discharges from ships and industrial activities have serious impacts on the environment and human health. In this study, a class of easy-to-synthesize polyethylenimine (PEI)-coated Fe3O4 magnetic nanoparticles (MNPs) was successfully synthesized via a one-step coprecipitation method. The synthesized PEI-coated Fe3O4 MNPs were characterized by using multiple technologies and applied in emulsified oil-water separation for the first time. It was found that the PEI effectively tuned the surface charge and wettability of MNPs. As a result, the PEI-coated MNPs could successfully assemble at the oil-water interface and promote the coalescence of oil droplets, thereby facilitating the subsequent magnetic separation. Results showed that the oil-water separation performance was superior and enhanced with the increase of ionic strength. Recycling experiment indicated that the PEI-coated MNPs could be reused up to six times without showing a significant decrease in separation efficiency. All of these results suggested that the PEI-coated MNP could potentially be used as a class of promising nanomaterials for emulsified oil-water separation. [Figure not available: see fulltext.

Interactions of endosulfan and methoxychlor involving CYP3A4 and CYP2B6 in human HepaRG cells.

PubMed

Savary, Camille C; Jossé, Rozenn; Bruyère, Arnaud; Guillet, Fabrice; Robin, Marie-Anne; Guillouzo, André

2014-08-01

Humans are usually exposed to several pesticides simultaneously; consequently, combined actions between pesticides themselves or between pesticides and other chemicals need to be addressed in the risk assessment. Many pesticides are efficient activators of pregnane X receptor (PXR) and/or constitutive androstane receptor (CAR), two major nuclear receptors that are also activated by other substrates. In the present work, we searched for interactions between endosulfan and methoxychlor, two organochlorine pesticides whose major routes of metabolism involve CAR- and PXR-regulated CYP3A4 and CYP2B6, and whose mechanisms of action in humans remain poorly understood. For this purpose, HepaRG cells were treated with both pesticides separately or in mixture for 24 hours or 2 weeks at concentrations relevant to human exposure levels. In combination they exerted synergistic cytotoxic effects. Whatever the duration of treatment, both compounds increased CYP3A4 and CYP2B6 mRNA levels while differently affecting their corresponding activities. Endosulfan exerted a direct reversible inhibition of CYP3A4 activity that was confirmed in human liver microsomes. By contrast, methoxychlor induced this activity. The effects of the mixture on CYP3A4 activity were equal to the sum of those of each individual compound, suggesting an additive effect of each pesticide. Despite CYP2B6 activity being unchanged and increased with endosulfan and methoxychlor, respectively, no change was observed with their mixture, supporting an antagonistic effect. Altogether, our data suggest that CAR and PXR activators endosulfan and methoxychlor can interact together and with other exogenous substrates in human hepatocytes. Their effects on CYP3A4 and CYP2B6 activities could have important consequences if extrapolated to the in vivo situation. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

[Study on the chemical components, antimicrobial and antitumor activities of the essential oil from the leaves of Zanthoxylum avicennae].

PubMed

Zhang, Da-Shuai; Zhong, Qiong-Xin; Song, Xin-Ming; Liu, Wen-Jie; Wang, Jing; Zhang, Qiong-Yu

2012-08-01

To study the chemical constituents, antimicrobial activity and antitumor activity of the essential oil from Zanthoxylum avicennae. The essential oil from the leaves of Zanthoxylum avicennae was extracted by steam distillation. The components of the essential oil were separated and identified by GC-MS. 72 components were identified and accounted for 98.15% of the all peak area. The essential oil exhibited strong antitumor activity against K-562 human tumor cell lines with IC50 of 1.76 microg/mL. It also exhibited moderate antimicrobial activity against three bacteria. The essential oil of Zanthoxylum avicennae contains various active constituents. This result provides scientific reference for the pharmacological further research of Zanthoxylum avicennae.

Evidence for a bimodal distribution in human communication.

PubMed

Wu, Ye; Zhou, Changsong; Xiao, Jinghua; Kurths, Jürgen; Schellnhuber, Hans Joachim

2010-11-02

Interacting human activities underlie the patterns of many social, technological, and economic phenomena. Here we present clear empirical evidence from Short Message correspondence that observed human actions are the result of the interplay of three basic ingredients: Poisson initiation of tasks and decision making for task execution in individual humans as well as interaction among individuals. This interplay leads to new types of interevent time distribution, neither completely Poisson nor power-law, but a bimodal combination of them. We show that the events can be separated into independent bursts which are generated by frequent mutual interactions in short times following random initiations of communications in longer times by the individuals. We introduce a minimal model of two interacting priority queues incorporating the three basic ingredients which fits well the distributions using the parameters extracted from the empirical data. The model can also embrace a range of realistic social interacting systems such as e-mail and letter communications when taking the time scale of processing into account. Our findings provide insight into various human activities both at the individual and network level. Our analysis and modeling of bimodal activity in human communication from the viewpoint of the interplay between processes of different time scales is likely to shed light on bimodal phenomena in other complex systems, such as interevent times in earthquakes, rainfall, forest fire, and economic systems, etc.

Evidence for a bimodal distribution in human communication

PubMed Central

Wu, Ye; Zhou, Changsong; Xiao, Jinghua; Kurths, Jürgen; Schellnhuber, Hans Joachim

2010-01-01

Interacting human activities underlie the patterns of many social, technological, and economic phenomena. Here we present clear empirical evidence from Short Message correspondence that observed human actions are the result of the interplay of three basic ingredients: Poisson initiation of tasks and decision making for task execution in individual humans as well as interaction among individuals. This interplay leads to new types of interevent time distribution, neither completely Poisson nor power-law, but a bimodal combination of them. We show that the events can be separated into independent bursts which are generated by frequent mutual interactions in short times following random initiations of communications in longer times by the individuals. We introduce a minimal model of two interacting priority queues incorporating the three basic ingredients which fits well the distributions using the parameters extracted from the empirical data. The model can also embrace a range of realistic social interacting systems such as e-mail and letter communications when taking the time scale of processing into account. Our findings provide insight into various human activities both at the individual and network level. Our analysis and modeling of bimodal activity in human communication from the viewpoint of the interplay between processes of different time scales is likely to shed light on bimodal phenomena in other complex systems, such as interevent times in earthquakes, rainfall, forest fire, and economic systems, etc. PMID:20959414

Chimpanzees' Context-Dependent Tool Use Provides Evidence for Separable Representations of Hand and Tool Even during Active Use within Peripersonal Space

ERIC Educational Resources Information Center

Povinelli, Daniel J.; Reaux, James E.; Frey, Scott H.

2010-01-01

Considerable attention has been devoted to behaviors in which tools are used to perform actions in extrapersonal space by extending the reach. Evidence suggests that these behaviors result in an expansion of the body schema and peripersonal space. However, humans often use tools to perform tasks within peripersonal space that cannot be…

Pilot Subjective Assessments During an Investigation of Separation Function Allocation Using a Human-In-The-Loop Simulation

NASA Technical Reports Server (NTRS)

Burke, Kelly A.; Wing, David J.; Lewis, Timothy

2013-01-01

Two human-in-the-loop simulation experiments were conducted to investigate allocation of separation assurance functions between ground and air and between humans and automation. The experiments modeled a mixed-operations concept in which aircraft receiving ground-based separation services shared the airspace with aircraft providing their own separation service (i.e., self-separation). The two experiments, one pilot-focused and the other controller-focused, addressed selected key issues of mixed operations and modeling an emergence of NextGen technologies and procedures. This paper focuses on the results of the subjective assessments of pilots collected during the pilot-focused human-in-the-loop simulation, specifically workload and situation awareness. Generally the results revealed that across all conditions, pilots' perceived workload was low to medium, with the highest reported levels of workload occurring when the pilots experienced a loss of separation during the scenario. Furthermore, the results from the workload data and situation awareness data were complimentary such that when pilots reported lower levels of workload they also experienced higher levels of situation awareness.

High-throughput, low-loss, low-cost, and label-free cell separation using electrophysiology-activated cell enrichment.

PubMed

Faraghat, Shabnam A; Hoettges, Kai F; Steinbach, Max K; van der Veen, Daan R; Brackenbury, William J; Henslee, Erin A; Labeed, Fatima H; Hughes, Michael P

2017-05-02

Currently, cell separation occurs almost exclusively by density gradient methods and by fluorescence- and magnetic-activated cell sorting (FACS/MACS). These variously suffer from lack of specificity, high cell loss, use of labels, and high capital/operating cost. We present a dielectrophoresis (DEP)-based cell-separation method, using 3D electrodes on a low-cost disposable chip; one cell type is allowed to pass through the chip whereas the other is retained and subsequently recovered. The method advances usability and throughput of DEP separation by orders of magnitude in throughput, efficiency, purity, recovery (cells arriving in the correct output fraction), cell losses (those which are unaccounted for at the end of the separation), and cost. The system was evaluated using three example separations: live and dead yeast; human cancer cells/red blood cells; and rodent fibroblasts/red blood cells. A single-pass protocol can enrich cells with cell recovery of up to 91.3% at over 300,000 cells per second with >3% cell loss. A two-pass protocol can process 300,000,000 cells in under 30 min, with cell recovery of up to 96.4% and cell losses below 5%, an effective processing rate >160,000 cells per second. A three-step protocol is shown to be effective for removal of 99.1% of RBCs spiked with 1% cancer cells while maintaining a processing rate of ∼170,000 cells per second. Furthermore, the self-contained and low-cost nature of the separator device means that it has potential application in low-contamination applications such as cell therapies, where good manufacturing practice compatibility is of paramount importance.

Neural correlates of learning in an electrocorticographic motor-imagery brain-computer interface

PubMed Central

Blakely, Tim M.; Miller, Kai J.; Rao, Rajesh P. N.; Ojemann, Jeffrey G.

2014-01-01

Human subjects can learn to control a one-dimensional electrocorticographic (ECoG) brain-computer interface (BCI) using modulation of primary motor (M1) high-gamma activity (signal power in the 75–200 Hz range). However, the stability and dynamics of the signals over the course of new BCI skill acquisition have not been investigated. In this study, we report 3 characteristic periods in evolution of the high-gamma control signal during BCI training: initial, low task accuracy with corresponding low power modulation in the gamma spectrum, followed by a second period of improved task accuracy with increasing average power separation between activity and rest, and a final period of high task accuracy with stable (or decreasing) power separation and decreasing trial-to-trial variance. These findings may have implications in the design and implementation of BCI control algorithms. PMID:25599079

An improved method for purification of recombinant truncated heme oxygenase-1 by expanded bed adsorption and gel filtration.

PubMed

Hu, Hong-Bo; Wang, Wei; Han, Ling; Zhou, Wen-Pu; Zhang, Xue-Hong

2007-03-01

Recombinant truncated human heme oxygenase-1 (hHO-1) expressed in Escherichia coli was efficiently separated and purified from feedstock by DEAE-ion exchange expanded bed adsorption. Protocol optimization of hHO-1 on DEAE adsorbent resulted in adsorption in 0 M NaCl and elution in 150 mM NaCl at a pH of 8.5. The active enzyme fractions separated from the expanded bed column were further purified by a Superdex 75 gel filtration step. The specific hHO-1 activity increased from 0.82 +/- 0.05 to 24.8 +/- 1.8 U/mg during the whole purification steps. The recovery and purification factor of truncated hHO-1 of the whole purification were 72.7 +/- 4.7 and 30.2 +/- 2.3%, respectively. This purification process can decrease the demand on the preparation of feedstock and simplify the purification process.

20 CFR 404.1325 - Separation from active service under conditions other than dishonorable.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Separation from active service under... of the Uniformed Services Separation from Active Service § 404.1325 Separation from active service under conditions other than dishonorable. Separation from active service under conditions other than...

20 CFR 404.1325 - Separation from active service under conditions other than dishonorable.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Separation from active service under... of the Uniformed Services Separation from Active Service § 404.1325 Separation from active service under conditions other than dishonorable. Separation from active service under conditions other than...

20 CFR 404.1325 - Separation from active service under conditions other than dishonorable.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Separation from active service under... of the Uniformed Services Separation from Active Service § 404.1325 Separation from active service under conditions other than dishonorable. Separation from active service under conditions other than...

20 CFR 404.1325 - Separation from active service under conditions other than dishonorable.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Separation from active service under... of the Uniformed Services Separation from Active Service § 404.1325 Separation from active service under conditions other than dishonorable. Separation from active service under conditions other than...

20 CFR 404.1325 - Separation from active service under conditions other than dishonorable.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Separation from active service under... of the Uniformed Services Separation from Active Service § 404.1325 Separation from active service under conditions other than dishonorable. Separation from active service under conditions other than...

EMG analysis of human postural responses during parabolic flight microgravity episodes

NASA Technical Reports Server (NTRS)

Layne, Charles S.; Spooner, Brian S.

1990-01-01

Anticipatory postural activity in the trunk and legs precedes rapid shoulder flexion in unit gravity. The hypothesis that anticipatory activity is a component of a single neural command for arm movement was tested by monitoring the surface electromyographic activity of the biceps femoris, paraspinals, and deltoid muscles of three subjects during the microgravity phase of parabolic flight. If part of a single command, anticipatory postural activity would be expected to remain intact despite the absence of the body's center of gravity in a reduced gravity environment. However, in at least 75 percent of the microgravity trials anticipatory biceps femoris activity was absent, indicating a separation of postural and agonist muscle activity. Such a finding suggests that anticipatory postural biceps femoris activity may be initiated independently of agonist (deltoid) activity.

Spike avalanches in vivo suggest a driven, slightly subcritical brain state

PubMed Central

Priesemann, Viola; Wibral, Michael; Valderrama, Mario; Pröpper, Robert; Le Van Quyen, Michel; Geisel, Theo; Triesch, Jochen; Nikolić, Danko; Munk, Matthias H. J.

2014-01-01

In self-organized critical (SOC) systems avalanche size distributions follow power-laws. Power-laws have also been observed for neural activity, and so it has been proposed that SOC underlies brain organization as well. Surprisingly, for spiking activity in vivo, evidence for SOC is still lacking. Therefore, we analyzed highly parallel spike recordings from awake rats and monkeys, anesthetized cats, and also local field potentials from humans. We compared these to spiking activity from two established critical models: the Bak-Tang-Wiesenfeld model, and a stochastic branching model. We found fundamental differences between the neural and the model activity. These differences could be overcome for both models through a combination of three modifications: (1) subsampling, (2) increasing the input to the model (this way eliminating the separation of time scales, which is fundamental to SOC and its avalanche definition), and (3) making the model slightly sub-critical. The match between the neural activity and the modified models held not only for the classical avalanche size distributions and estimated branching parameters, but also for two novel measures (mean avalanche size, and frequency of single spikes), and for the dependence of all these measures on the temporal bin size. Our results suggest that neural activity in vivo shows a mélange of avalanches, and not temporally separated ones, and that their global activity propagation can be approximated by the principle that one spike on average triggers a little less than one spike in the next step. This implies that neural activity does not reflect a SOC state but a slightly sub-critical regime without a separation of time scales. Potential advantages of this regime may be faster information processing, and a safety margin from super-criticality, which has been linked to epilepsy. PMID:25009473

Species-specific calls evoke asymmetric activity in the monkey's temporal poles.

PubMed

Poremba, Amy; Malloy, Megan; Saunders, Richard C; Carson, Richard E; Herscovitch, Peter; Mishkin, Mortimer

2004-01-29

It has often been proposed that the vocal calls of monkeys are precursors of human speech, in part because they provide critical information to other members of the species who rely on them for survival and social interactions. Both behavioural and lesion studies suggest that monkeys, like humans, use the auditory system of the left hemisphere preferentially to process vocalizations. To investigate the pattern of neural activity that might underlie this particular form of functional asymmetry in monkeys, we measured local cerebral metabolic activity while the animals listened passively to species-specific calls compared with a variety of other classes of sound. Within the superior temporal gyrus, significantly greater metabolic activity occurred on the left side than on the right, only in the region of the temporal pole and only in response to monkey calls. This functional asymmetry was absent when these regions were separated by forebrain commissurotomy, suggesting that the perception of vocalizations elicits concurrent interhemispheric interactions that focus the auditory processing within a specialized area of one hemisphere.

Antifungal activity of different neem leaf extracts and the nimonol against some important human pathogens

PubMed Central

Mahmoud, D.A.; Hassanein, N.M.; Youssef, K.A.; Abou Zeid, M.A.

2011-01-01

This study was conducted to evaluate the effect of aqueous, ethanolic and ethyl acetate extracts from neem leaves on growth of some human pathogens (Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus, Candida albicans and Microsporum gypseum) in vitro. Different concentrations (5, 10, 15 and 20%) prepared from these extracts inhibited the growth of the test pathogens and the effect gradually increased with concentration. The 20% ethyl acetate extract gave the strongest inhibition compared with the activity obtained by the same concentration of the other extracts. High Performance Liquid Chromatography (HPLC) analysis of ethyl acetate extract showed the presence of a main component (nimonol) which was purified and chemically confirmed by Nuclear Magnetic Resonance (NMR) spectroscopic analysis. The 20% ethyl acetate extract lost a part of its antifungal effect after pooling out the nimonol and this loss in activity was variable on test pathogens. The purified nimonol as a separate compound did not show any antifungal activity when assayed against all the six fungal pathogens. PMID:24031718

Chiral analysis of bambuterol, its intermediate and active drug in human plasma by liquid chromatography-tandem mass spectrometry: Application to a pharmacokinetic study.

PubMed

Zhou, Ting; Liu, Shan; Zhao, Ting; Zeng, Jing; He, Mingzhi; Xu, Beining; Qu, Shanshan; Xu, Ling; Tan, Wen

2015-08-01

A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for simultaneous chiral analysis of an antiasthma drug bambuterol, its key intermediate monocarbamate bambuterol and its active drug terbutaline in human plasma. All samples were extracted with ethyl acetate and separated on an Astec Chirobiotic T column under isocratic elution with a mobile phase consisting of methanol and water with the addition of 20mm ammonium acetate and 0.005% (v/v) formic acid at 0.6mL/min. The analytes were detected by a Xevo TQ-S tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method has high sensitivity with the lower limit of quantifications of 25.00pg/mL for bambuterol enantiomers, and 50.00pg/mL for monocarbamate bambuterol and terbutaline enantiomers, respectively. The calibration curves for bambuterol enantiomers were linear in the range of 25.00-2500pg/mL, and for monocarbamate bambuterol and terbutaline enantiomers were linear in the range of 50.00-5000pg/mL. The intra- and inter-day precisions were <12.4%. All the analytes were separated in 18.0min. For the first time, the validated method was successfully applied to an enantioselective pharmacokinetic study of rac-bambuterol in 8 healthy volunteers. According to the results, this chiral LC-MS/MS assay provides a suitable and robust method for the enantioselectivity and interaction study of the prodrug bambuterol, the key intermediate monocarbamate bambuterol and its active drug terbutaline in human. Copyright © 2015 Elsevier B.V. All rights reserved.

Hanford Immobilized Low Activity Waste (ILAW) Performance Assessment 2001 Version [Formerly DOE/RL-97-69] [SEC 1 & 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

MANN, F.M.

2000-08-01

The Hanford Immobilized Low-Activity Waste Performance Assessment examines the long-term environmental and human health effects associated with the planned disposal of the vitrified low-activity fraction of waste presently contained in Hanford Site tanks. The tank waste is the byproduct of separating special nuclear materials from irradiated nuclear fuels over the past 50 years. This waste is stored in underground single- and double-shell tanks. The tank waste is to be retrieved, separated into low-activity and high-level fractions, and then immobilized by vitrification. The US. Department of Energy (DOE) plans to dispose of the low-activity fraction in the Hanford Site 200 Eastmore » Area. The high-level fraction will be stored at the Hanford Site until a national repository is approved. This report provides the site-specific long-term environmental information needed by the DOE to modify the current Disposal Authorization Statement for the Hanford Site that would allow the following: construction of disposal trenches; and filling of these trenches with ILAW containers and filler material with the intent to dispose of the containers.« less

Lost Horizons: The Humanities in South Africa (Part 1)

ERIC Educational Resources Information Center

Vale, Peter

2008-01-01

Politics chartered the development of the Humanities in South Africa. Under the apartheid system three separate traditions--English-speaking, Afrikaner and Homeland--co-existed, albeit uneasily, in separate institutional forms. As apartheid crumbled in the 1980s, the Humanities, by drawing the three traditions together, established a growing voice…

Human, Nature, Dynamism: The Effects of Content and Movement Perception on Brain Activations during the Aesthetic Judgment of Representational Paintings

PubMed Central

Di Dio, Cinzia; Ardizzi, Martina; Massaro, Davide; Di Cesare, Giuseppe; Gilli, Gabriella; Marchetti, Antonella; Gallese, Vittorio

2016-01-01

Movement perception and its role in aesthetic experience have been often studied, within empirical aesthetics, in relation to the human body. No such specificity has been defined in neuroimaging studies with respect to contents lacking a human form. The aim of this work was to explore, through functional magnetic imaging (f MRI), how perceived movement is processed during the aesthetic judgment of paintings using two types of content: human subjects and scenes of nature. Participants, untutored in the arts, were shown the stimuli and asked to make aesthetic judgments. Additionally, they were instructed to observe the paintings and to rate their perceived movement in separate blocks. Observation highlighted spontaneous processes associated with aesthetic experience, whereas movement judgment outlined activations specifically related to movement processing. The ratings recorded during aesthetic judgment revealed that nature scenes received higher scored than human content paintings. The imaging data showed similar activation, relative to baseline, for all stimuli in the three tasks, including activation of occipito-temporal areas, posterior parietal, and premotor cortices. Contrast analyses within aesthetic judgment task showed that human content activated, relative to nature, precuneus, fusiform gyrus, and posterior temporal areas, whose activation was prominent for dynamic human paintings. In contrast, nature scenes activated, relative to human stimuli, occipital and posterior parietal cortex/precuneus, involved in visuospatial exploration and pragmatic coding of movement, as well as central insula. Static nature paintings further activated, relative to dynamic nature stimuli, central and posterior insula. Besides insular activation, which was specific for aesthetic judgment, we found a large overlap in the activation pattern characterizing each stimulus dimension (content and dynamism) across observation, aesthetic judgment, and movement judgment tasks. These findings support the idea that the aesthetic evaluation of artworks depicting both human subjects and nature scenes involves a motor component, and that the associated neural processes occur quite spontaneously in the viewer. Furthermore, considering the functional roles of posterior and central insula, we suggest that nature paintings may evoke aesthetic processes requiring an additional proprioceptive and sensori-motor component implemented by “motor accessibility” to the represented scenario, which is needed to judge the aesthetic value of the observed painting. PMID:26793087

Isolation of purified oocyst walls and sporocysts from Toxoplasma gondii.

PubMed

Everson, William V; Ware, Michael W; Dubey, J P; Lindquist, H D Alan

2002-01-01

Toxoplasma gondii oocysts are environmentally resistant and can infect virtually all warm-blooded hosts, including humans and livestock. Little is known about the biochemical basis for this resistance of oocysts, and mechanism for excystation of T. gondii sporozoites. The objective of the present study was to evaluate different methods (mechanical fragmentation, gradients, flow cytometry) to separate and purify T. gondii oocyst walls and sporocysts. Oocyst walls were successfully separated and purified using iodixanol gradients. Sporocysts were successfully separated and purified using iodixanol and Percoll gradients. Purification was also achieved by flow cytometry. Flow cytometry with fluorescence-activated cell sorting (FACS) yielded analytical quantities of oocyst walls and intact sporocysts. Flow cytometry with FACS also proved useful for quantitation of purity obtained following iodixanol gradient fractionation. Methods reported in this paper will be useful for analytical purposes, such as proteomic analysis of components unique to this life cycle stage, development of detection methods, or excystation studies.

Ideology as instrument.

PubMed

Glassman, Michael; Karno, Donna

2007-12-01

Comments on the article by J. T. Jost, which argued that the end-of-ideology claims that emerged in the aftermath of World War II were both incorrect and detrimental to the field of political psychology. M. Glassman and D. Karno make three critical points. First, Jost objectified ideology as a grand strategy implemented at the individual level, rather than as an instrument used for a specific purpose in activity. In doing so, he set ideology up as an "object" that guides human behavior rather than as a rational part of human experience. Second, they take issue with the idea that, because somebody acts in a manner that can be categorized as ideological, there actually is such a thing as ideology separate from that event and/or political experience and that psychologists ought to understand the meaning of ideology in order to understand future human activities as outside observers. Third, Jost seems to see this objective ideology as a unidirectional, causal mechanism for activity, a mechanism that assumes individuals act according to ideology, which eclipses the possibility that immediate ideological positions are the residue of purposeful activity. Glassman and Karno suggest that it may be better to take a pluralistic view of ideology in human action. Where ideology does exist, it is as a purposeful instrument--part of a logically based action to meet some ends-in-view--a mixture of immediate goals tied to secondary belief systems (which have been integrated to serve the material purposes of the purveyors of these ideologies). So if we are to understand ideology, we can only understand it through its use in human activity. (Copyright) 2007 APA.

Betaine:homocysteine methyltransferase--a new assay for the liver enzyme and its absence from human skin fibroblasts and peripheral blood lymphocytes.

PubMed

Wang, J A; Dudman, N P; Lynch, J; Wilcken, D E

1991-12-31

Chronic elevation of plasma homocysteine is associated with increased atherogenesis and thrombosis, and can be lowered by betaine (N,N,N-trimethylglycine) treatment which is thought to stimulate activity of the enzyme betaine:homocysteine methyltransferase. We have developed a new assay for this enzyme, in which the products of the enzyme-catalysed reaction between betaine and homocysteine are oxidised by performic acid before being separated and quantified by amino acid analysis. This assay confirmed that human liver contains abundant betaine:homocysteine methyltransferase (33.4 nmol/h/mg protein at 37 degrees C, pH 7.4). Chicken and lamb livers also contain the enzyme, with respective activities of 50.4 and 6.2 nmol/h/mg protein. However, phytohaemagglutinin-stimulated human peripheral blood lymphocytes and cultured human skin fibroblasts contained no detectable betaine:homocysteine methyltransferase (less than 1.4 nmol/h/mg protein), even after cells were pre-cultured in media designed to stimulate production of the enzyme. The results emphasize the importance of the liver in mediating the lowering of elevated circulating homocysteine by betaine.

Sticky-flares for in situ monitoring of human telomerase RNA in living cells.

PubMed

Wu, Qilong; Liu, Zhengjie; Su, Lei; Han, Guangmei; Liu, Renyong; Zhao, Jun; Zhao, Tingting; Jiang, Changlong; Zhang, Zhongping

2018-05-17

Human telomerase RNA (hTR), a template of telomerase for telomeric repeat synthesis, was used to reflect the telomerase activity and act as a potential target of antitumor therapy. Here, we report a novel DNA-conjugated AuNP probe termed sticky-flares for the in situ detection of intracellular human telomerase RNA. The sticky-flares probe is capable of entering living cells directly without any auxiliary and recognizing the binding domain of human telomerase RNA. On recognition, the fluorophore-modified recognition flares can specifically bind to the target, separate from the sticky-flares and act as a fluorescent reporter to quantify and dynamically profile human telomerase RNA in living cells. We envision that the sticky-flares probe would be a valuable platform to investigate the function and regulation of hTR in antitumor therapy and hTR-related drug invention.

Purification of high-molecular-weight subfraction from porcine skin inhibiting proliferation of A431 human carcinoma epidermoid cells.

PubMed

Belova, O V; Sergienko, V I; Arion, V Ya; Lukanidina, T A; Moskvina, S N; Zimina, I V; Borisenko, G G; Lutsenko, G V; Grechikhina, M V; Kovaleva, E V; Klyuchnikova, Zh I

2014-07-01

Subfraction with a molecular weight >250 kDa isolated from porcine skin and inhibiting the proliferation of A431 human carcinoma epidermoid cells was purified by DEAE 32 anion exchange chromatography with NaCl concentration step-gradient. The effects of the initial subfraction and fractions obtained by separation in DEAE 32 on the proliferation of A431 human carcinoma epidermoid cells were studied in vitro in two tests (MTT and fluorescent test). The more sensitive fluorescent test showed the highest inhibitory activity of fraction No. 2 released from the column at 0.15 M NaCl. One major protein component and a series of minor protein components were detected in this fraction by vertical PAAG-SDS electrophoresis.

An Approach to Using Toxicogenomic Data in US EPA Human ...

EPA Pesticide Factsheets

EPA announced the availability of the final report, An Approach to Using Toxicogenomic Data in U.S. EPA Human Health Risk Assessments: A Dibutyl Phthalate Case Study. This report outlines an approach to evaluate genomic data for use in risk assessment and a case study to illustrate the approach. The dibutyl phthalate (DBP) case study example focuses on male reproductive developmental effects and the qualitative application of genomic data because of the available data on DBP. The case study presented in this report is a separate activity from any of the ongoing IRIS human health assessments for the phthalates. The National Center for Environmental Assessment (NCEA) prepared this document for the purpose of describing and illustrating an approach for using toxicogenomic data in risk assessment.

Inference of the Activity Timeline of Cattle Foraging on a Mediterranean Woodland Using GPS and Pedometry

PubMed Central

Ungar, Eugene D.; Schoenbaum, Iris; Henkin, Zalmen; Dolev, Amit; Yehuda, Yehuda; Brosh, Arieh

2011-01-01

The advent of the Global Positioning System (GPS) has transformed our ability to track livestock on rangelands. However, GPS data use would be greatly enhanced if we could also infer the activity timeline of an animal. We tested how well animal activity could be inferred from data provided by Lotek GPS collars, alone or in conjunction with IceRobotics IceTag pedometers. The collars provide motion and head position data, as well as location. The pedometers count steps, measure activity levels, and differentiate between standing and lying positions. We gathered synchronized data at 5-min resolution, from GPS collars, pedometers, and human observers, for free-grazing cattle (n = 9) at the Hatal Research Station in northern Israel. Equations for inferring activity during 5-min intervals (n = 1,475), classified as Graze, Rest (or Lie and Stand separately), and Travel were derived by discriminant and partition (classification tree) analysis of data from each device separately and from both together. When activity was classified as Graze, Rest and Travel, the lowest overall misclassification rate (10%) was obtained when data from both devices together were subjected to partition analysis; separate misclassification rates were 8, 12, and 3% for Graze, Rest and Travel, respectively. When Rest was subdivided into Lie and Stand, the lowest overall misclassification rate (10%) was again obtained when data from both devices together were subjected to partition analysis; misclassification rates were 6, 1, 26, and 17% for Graze, Lie, Stand, and Travel, respectively. The primary problem was confusion between Rest (or Stand) and Graze. Overall, the combination of Lotek GPS collars with IceRobotics IceTag pedometers was found superior to either device alone in inferring animal activity. PMID:22346582

Functional characterization of a regulatory human T-cell subpopulation increasing during autologous MLR.

PubMed Central

Cosulich, M E; Risso, A; Canonica, G W; Bargellesi, A

1986-01-01

The present study was undertaken to investigate the heterogeneity of helper T cells in humans using two different monoclonal antibodies: 5/9 and MLR4. The former identifies 15-20% of resting T lymphocytes from peripheral blood and corresponds to an anti-helper/inducer T cell. The second antibody, MLR4, recognizes 5% of total T lymphocytes and partially overlaps with the 5/9+ T cells. In order to investigate functional differences within the 5/9+ cells, we separated two different subsets (5/9+ MLR+ and 5/9+ MLR4-) by a rosetting technique. Although both subsets provide help for Ig synthesis in a PWM-stimulated culture, only the 5/9+ MLR4- fraction gave a proliferative response in both autologous and allogeneic MLR and to soluble protein antigens. The effect of radiation on the ability of the two subsets to provide help for Ig synthesis showed that the 5/9+ MLR4+ subset is highly radiation-sensitive, while 5/9+ MLR- is relatively radiation-resistant. In a further series of experiments, 5/9+ MLR4+ cells isolated after activation in an autologous MLR but not by Con A, were no longer able to induce T-cell differentiation but now showed a strong suppressor effect. The 5/9+ MLR4- subset separated from the same cultures did not display any suppressor function. These data demonstrate in fresh PBL the existence of a radiation-sensitive regulatory subset exerting a helper activity, and which acquires suppressor activity after activation in autologous MLR. PMID:2936679

Detection and characterisation of Complement protein activity in bovine milk by bactericidal sequestration assay.

PubMed

Maye, Susan; Stanton, Catherine; Fitzgerald, Gerald F; Kelly, Philip M

2015-08-01

While the Complement protein system in human milk is well characterised, there is little information on its presence and activity in bovine milk. Complement forms part of the innate immune system, hence the importance of its contribution during milk ingestion to the overall defences of the neonate. A bactericidal sequestration assay, featuring a Complement sensitive strain, Escherichia coli 0111, originally used to characterise Complement activity in human milk was successfully applied to freshly drawn bovine milk samples, thus, providing an opportunity to compare Complement activities in both human and bovine milks. Although not identical in response, the levels of Complement activity in bovine milk were found to be closely comparable with that of human milk. Differential counts of Esch. coli 0111 after 2 h incubation were 6.20 and 6.06 log CFU/ml, for raw bovine and human milks, respectively - the lower value representing a stronger Complement response. Exposing bovine milk to a range of thermal treatments e.g. 42, 45, 65, 72, 85 or 95 °C for 10 min, progressively inhibited Complement activity by increasing temperature, thus confirming the heat labile nature of this immune protein system. Low level Complement activity was found, however, in 65 and 72 °C heat treated samples and in retailed pasteurised milk which highlights the outer limit to which high temperature, short time (HTST) industrial thermal processes should be applied if retention of activity is a priority. Concentration of Complement in the fat phase was evident following cream separation, and this was also reflected in the further loss of activity recorded in low fat variants of retailed pasteurised milk. Laboratory-based churning of the cream during simulated buttermaking generated an aqueous (buttermilk) phase with higher levels of Complement activity than the fat phase, thus pointing to a likely association with the milk fat globule membrane (MFGM) layer.

The P2Y12 Antagonists, 2-Methylthioadenosine 5′-Monophosphate Triethylammonium Salt and Cangrelor (ARC69931MX), Can Inhibit Human Platelet Aggregation through a Gi-independent Increase in cAMP Levels*

PubMed Central

Srinivasan, Subhashini; Mir, Fozia; Huang, Jin-Sheng; Khasawneh, Fadi T.; Lam, Stephen C.-T.; Le Breton, Guy C.

2009-01-01

ADP plays an integral role in the process of hemostasis by signaling through two platelet G-protein-coupled receptors, P2Y1 and P2Y12. The recent use of antagonists against these two receptors has contributed a substantial body of data characterizing the ADP signaling pathways in human platelets. Specifically, the results have indicated that although P2Y1 receptors are involved in the initiation of platelet aggregation, P2Y12 receptor activation appears to account for the bulk of the ADP-mediated effects. Based on this consideration, emphasis has been placed on the development of a new class of P2Y12 antagonists (separate from clopidogrel and ticlopidine) as an approach to the treatment of thromboembolic disorders. The present work examined the molecular mechanisms by which two of these widely used adenosine-based P2Y12 antagonists (2-methylthioadenosine 5′-monophosphate triethylammonium salt (2MeSAMP) and ARC69931MX), inhibit human platelet activation. It was found that both of these compounds raise platelet cAMP to levels that substantially inhibit platelet aggregation. Furthermore, the results demonstrated that this elevation of cAMP did not require Gi signaling or functional P2Y12 receptors but was mediated through activation of a separate G protein-coupled pathway, presumably involving Gs. However, additional experiments revealed that neither 2MeSAMP nor ARC69931MX (cangrelor) increased cAMP through activation of A2a, IP, DP, or EP2 receptors, which are known to couple to Gs. Collectively, these findings indicate that 2MeSAMP and ARC69931MX interact with an unidentified platelet G protein-coupled receptor that stimulates cAMP-mediated inhibition of platelet function. This inhibition is in addition to that derived from antagonism of P2Y12 receptors. PMID:19346255

Electrophoretic cell separation by means of microspheres

NASA Technical Reports Server (NTRS)

Smolka, A. J. K.; Nerren, B. H.; Margel, S.; Rembaum, A.

1979-01-01

The electrophoretic mobility of fixed human erythrocytes immunologically labeled with poly(vinylpyridine) or poly(glutaraldehyde) microspheres was reduced by approximately 40%. This observation was utilized in preparative scale electrophoretic separations of fixed human and turkey erythrocytes, the mobilities of which under normal physiological conditions do not differ sufficiently to allow their separation by continuous flow electrophoresis. We suggest that resolution in the electrophoretic separation of cell subpopulations, currently limited by finite and often overlapping mobility distributions, may be significantly enhanced by immunospecific labeling of target populations using microspheres.

Individual Differences in Spatial Pattern Separation Performance Associated with Healthy Aging in Humans

ERIC Educational Resources Information Center

Stark, Shauna M.; Yassa, Michael A.; Stark, Craig E. L.

2010-01-01

Rodent studies have suggested that "pattern separation," the ability to distinguish among similar experiences, is diminished in a subset of aged rats. We extended these findings to the human using a task designed to assess spatial pattern separation behavior (determining at time of test whether pairs of pictures shown during the study were in the…

Physiological activity of irradiated green tea polyphenol on the human skin.

PubMed

An, Bong-Jeun; Kwak, Jae-Hoon; Son, Jun-Ho; Park, Jung-Mi; Lee, Jin-Young; Park, Tae Soon; Kim, So-Yeun; Kim, Yeoung-Sun; Jo, Cheorun; Byun, Myung-Woo

2005-01-01

Physiological activity of irradiated green tea polyphenol on the human skin was investigated for further industrial application. The green tea polyphenol was separated and irradiated at 40 kGy by y-ray. For an anti-wrinkle effect, the collagenase inhibition effect was higher in the irradiated sample (65.3%) than that of the non-irradiated control (56.8%) at 200 ppm of the concentration (p < 0.05). Collagen biosynthesis rates using a human fibroblast were 19.4% and 16.3% in the irradiated and the non-irradiated polyphenols, respectively. The tyrosinase inhibition effect, which is related to the skin-whitening effect, showed a 45.2% and 42.9% in the irradiated and the non-irradiated polyphenols, respectively, at a 100 ppm level. A higher than 90% growth inhibition on skin cancer cells (SK-MEL-2 and G361) was demonstrated in both the irradiated and the non-irradiated polyphenols. Thus, the irradiation of green tea polyphenol did not change and even increased its anti-wrinkle, skin-whitening and anticancer effects on the human skin. The results indicated that irradiated green tea polyphenol can be used as a natural ingredient with excellent physiological functions for the human skin through cosmetic or food composition.

Converging PET and fMRI evidence for a common area involved in human focal epilepsies

PubMed Central

Laufs, H.; Richardson, M.P.; Salek-Haddadi, A.; Vollmar, C.; Duncan, J.S.; Gale, K.; Lemieux, L.; Löscher, W.

2011-01-01

Objectives: Experiments in animal models have identified specific subcortical anatomic circuits, which are critically involved in the pathogenesis and control of seizure activity. However, whether such anatomic substrates also exist in human epilepsy is not known. Methods: We studied 2 separate groups of patients with focal epilepsies arising from any cortical location using either simultaneous EEG-fMRI (n = 19 patients) or [11C]flumazenil PET (n = 18). Results: Time-locked with the interictal epileptiform discharges, we found significant hemodynamic increases common to all patients near the frontal piriform cortex ipsilateral to the presumed cortical focus. GABAA receptor binding in the same area was reduced in patients with more frequent seizures. Conclusions: Our findings of cerebral blood flow and GABAergic changes, irrespective of where interictal or ictal activity occurs in the cortex, suggest that this area of the human primary olfactory cortex may be an attractive new target for epilepsy therapy, including neurosurgery, electrical stimulation, and focal drug delivery. PMID:21849655

Analysis of Normal Human Mammary Epigenomes Reveals Cell-Specific Active Enhancer States and Associated Transcription Factor Networks.

PubMed

Pellacani, Davide; Bilenky, Misha; Kannan, Nagarajan; Heravi-Moussavi, Alireza; Knapp, David J H F; Gakkhar, Sitanshu; Moksa, Michelle; Carles, Annaick; Moore, Richard; Mungall, Andrew J; Marra, Marco A; Jones, Steven J M; Aparicio, Samuel; Hirst, Martin; Eaves, Connie J

2016-11-15

The normal adult human mammary gland is a continuous bilayered epithelial system. Bipotent and myoepithelial progenitors are prominent and unique components of the outer (basal) layer. The inner (luminal) layer includes both luminal-restricted progenitors and a phenotypically separable fraction that lacks progenitor activity. We now report an epigenomic comparison of these three subsets with one another, with their associated stromal cells, and with three immortalized, non-tumorigenic human mammary cell lines. Each genome-wide analysis contains profiles for six histone marks, methylated DNA, and RNA transcripts. Analysis of these datasets shows that each cell type has unique features, primarily within genomic regulatory regions, and that the cell lines group together. Analyses of the promoter and enhancer profiles place the luminal progenitors in between the basal cells and the non-progenitor luminal subset. Integrative analysis reveals networks of subset-specific transcription factors. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Discriminating Characteristics of Tectonic and Human-Induced Seismicity

NASA Astrophysics Data System (ADS)

Zaliapin, I. V.; Ben-Zion, Y.

2015-12-01

We analyze statistical features of background and clustered subpopulations of earthquakes in different regions in an effort to distinguish between human-induced and natural seismicity. Analysis of "end-member" areas known to be dominated by human-induced earthquakes (the Geyser geothermal field in northern California and TauTona gold mine in South Africa) and regular tectonic activity (the San Jacinto fault zone in southern California and Coso region excluding the Coso geothermal field in eastern central California) reveals several distinguishing characteristics. Induced seismicity is shown to have (i) higher rate of background events (both absolute and relative to the total rate), (ii) faster temporal offspring decay, (iii) higher intensity of repeating events, (iv) larger proportion of small clusters, and (v) larger spatial separation between parent and offspring, compared to regular tectonic activity. These differences also successfully discriminate seismicity within the Coso and Salton Sea geothermal fields in California before and after the expansion of geothermal production during the 1980s.

Two spatiotemporally distinct value systems shape reward-based learning in the human brain.

PubMed

Fouragnan, Elsa; Retzler, Chris; Mullinger, Karen; Philiastides, Marios G

2015-09-08

Avoiding repeated mistakes and learning to reinforce rewarding decisions is critical for human survival and adaptive actions. Yet, the neural underpinnings of the value systems that encode different decision-outcomes remain elusive. Here coupling single-trial electroencephalography with simultaneously acquired functional magnetic resonance imaging, we uncover the spatiotemporal dynamics of two separate but interacting value systems encoding decision-outcomes. Consistent with a role in regulating alertness and switching behaviours, an early system is activated only by negative outcomes and engages arousal-related and motor-preparatory brain structures. Consistent with a role in reward-based learning, a later system differentially suppresses or activates regions of the human reward network in response to negative and positive outcomes, respectively. Following negative outcomes, the early system interacts and downregulates the late system, through a thalamic interaction with the ventral striatum. Critically, the strength of this coupling predicts participants' switching behaviour and avoidance learning, directly implicating the thalamostriatal pathway in reward-based learning.

Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds

PubMed Central

Delfosse, Vanessa; Dendele, Béatrice; Huet, Tiphaine; Grimaldi, Marina; Boulahtouf, Abdelhay; Gerbal-Chaloin, Sabine; Beucher, Bertrand; Roecklin, Dominique; Muller, Christina; Rahmani, Roger; Cavaillès, Vincent; Daujat-Chavanieu, Martine; Vivat, Valérie; Pascussi, Jean-Marc; Balaguer, Patrick; Bourguet, William

2015-01-01

Humans are chronically exposed to multiple exogenous substances, including environmental pollutants, drugs and dietary components. Many of these compounds are suspected to impact human health, and their combination in complex mixtures could exacerbate their harmful effects. Here we demonstrate that a pharmaceutical oestrogen and a persistent organochlorine pesticide, both exhibiting low efficacy when studied separately, cooperatively bind to the pregnane X receptor, leading to synergistic activation. Biophysical analysis shows that each ligand enhances the binding affinity of the other, so the binary mixture induces a substantial biological response at doses at which each chemical individually is inactive. High-resolution crystal structures reveal the structural basis for the observed cooperativity. Our results suggest that the formation of ‘supramolecular ligands' within the ligand-binding pocket of nuclear receptors contributes to the synergistic toxic effect of chemical mixtures, which may have broad implications for the fields of endocrine disruption, toxicology and chemical risk assessment. PMID:26333997

Motivational sensitivity of outcome-response priming: Experimental research and theoretical models.

PubMed

Watson, Poppy; Wiers, Reinout W; Hommel, Bernhard; de Wit, Sanne

2018-02-21

Outcome-response (O-R) priming is at the core of various associative theories of human intentional action. This is a simple and parsimonious mechanism by which activation of outcome representations (e.g. thinking about the light coming on) leads to activation of the associated motor patterns required to achieve it (e.g. pushing the light switch). In the current manuscript, we review the evidence for such O-R associative links demonstrated by converging (yet until now, separate) strands of research. While there is a wealth of evidence that both the perceptual and motivational properties of an outcome can be encoded in the O-R association and mediate O-R priming, we critically examine the integration of these mechanisms and the conditions under which motivational factors constrain the sensory O-R priming effect. We discuss the clinical relevance of this O-R priming mechanism, whether it can satisfactorily account for human goal-directed behaviour, and the implications for theories of human action control.

An analytical approach to separate climate and human contributions to basin streamflow variability

NASA Astrophysics Data System (ADS)

Li, Changbin; Wang, Liuming; Wanrui, Wang; Qi, Jiaguo; Linshan, Yang; Zhang, Yuan; Lei, Wu; Cui, Xia; Wang, Peng

2018-04-01

Climate variability and anthropogenic regulations are two interwoven factors in the ecohydrologic system across large basins. Understanding the roles that these two factors play under various hydrologic conditions is of great significance for basin hydrology and sustainable water utilization. In this study, we present an analytical approach based on coupling water balance method and Budyko hypothesis to derive effectiveness coefficients (ECs) of climate change, as a way to disentangle contributions of it and human activities to the variability of river discharges under different hydro-transitional situations. The climate dominated streamflow change (ΔQc) by EC approach was compared with those deduced by the elasticity method and sensitivity index. The results suggest that the EC approach is valid and applicable for hydrologic study at large basin scale. Analyses of various scenarios revealed that contributions of climate change and human activities to river discharge variation differed among the regions of the study area. Over the past several decades, climate change dominated hydro-transitions from dry to wet, while human activities played key roles in the reduction of streamflow during wet to dry periods. Remarkable decline of discharge in upstream was mainly due to human interventions, although climate contributed more to runoff increasing during dry periods in the semi-arid downstream. Induced effectiveness on streamflow changes indicated a contribution ratio of 49% for climate and 51% for human activities at the basin scale from 1956 to 2015. The mathematic derivation based simple approach, together with the case example of temporal segmentation and spatial zoning, could help people understand variation of river discharge with more details at a large basin scale under the background of climate change and human regulations.

Evidence for the Existence of a Bone Marrow Blood Barrier for the Passage of Specific Committed Stem Cells in Human and Canine and Their Physical Separation from Lymphocytes and Pluripotent Stem Cells

DTIC Science & Technology

1982-11-12

COMWITTED STEM CELLS IN HUMANS AND CANINES AND THEIR PHYSICAL SEPARATION FROM LYMPHOCYTES AND PLURIPOTENT STEM CELLS Name of Candidate: Thomas J...Passage of Specific Committed Stem CeUs in Human and Canine and Their Physical Separation From Lymphocytes and Pluripotent Stem Cells Thomas Jose...principle of counterflow centrifugation elutriation (CCE) for the broader enunciation of this theory in the canine and to postulate a similar theory

The Kinesin-Related Protein, Hset, Opposes the Activity of Eg5 and Cross-Links Microtubules in the Mammalian Mitotic Spindle

PubMed Central

Mountain, Vicki; Simerly, Calvin; Howard, Louisa; Ando, Asako; Schatten, Gerald; Compton, Duane A.

1999-01-01

We have prepared antibodies specific for HSET, the human homologue of the KAR3 family of minus end-directed motors. Immuno-EM with these antibodies indicates that HSET frequently localizes between microtubules within the mammalian metaphase spindle consistent with a microtubule cross-linking function. Microinjection experiments show that HSET activity is essential for meiotic spindle organization in murine oocytes and taxol-induced aster assembly in cultured cells. However, inhibition of HSET did not affect mitotic spindle architecture or function in cultured cells, indicating that centrosomes mask the role of HSET during mitosis. We also show that (acentrosomal) microtubule asters fail to assemble in vitro without HSET activity, but simultaneous inhibition of HSET and Eg5, a plus end-directed motor, redresses the balance of forces acting on microtubules and restores aster organization. In vivo, centrosomes fail to separate and monopolar spindles assemble without Eg5 activity. Simultaneous inhibition of HSET and Eg5 restores centrosome separation and, in some cases, bipolar spindle formation. Thus, through microtubule cross-linking and oppositely oriented motor activity, HSET and Eg5 participate in spindle assembly and promote spindle bipolarity, although the activity of HSET is not essential for spindle assembly and function in cultured cells because of centrosomes. PMID:10525540

Improved recovery of the hemodynamic response in Diffuse Optical Imaging using short optode separations and state-space modeling

PubMed Central

Gagnon, Louis; Perdue, Katherine; Greve, Douglas N.; Goldenholz, Daniel; Kaskhedikar, Gayatri; Boas, David A.

2011-01-01

Diffuse Optical Imaging (DOI) allows the recovery of the hemodynamic response associated with evoked brain activity. The signal is contaminated with systemic physiological interference which occurs in the superficial layers of the head as well as in the brain tissue. The back-reflection geometry of the measurement makes the DOI signal strongly contaminated by systemic interference occurring in the superficial layers. A recent development has been the use of signals from small source-detector separation (1 cm) optodes as regressors. Since those additional measurements are mainly sensitive to superficial layers in adult humans, they help in removing the systemic interference present in longer separation measurements (3 cm). Encouraged by those findings, we developed a dynamic estimation procedure to remove global interference using small optode separations and to estimate simultaneously the hemodynamic response. The algorithm was tested by recovering a simulated synthetic hemodynamic response added over baseline DOI data acquired from 6 human subjects at rest. The performance of the algorithm was quantified by the Pearson R2 coefficient and the mean square error (MSE) between the recovered and the simulated hemodynamic responses. Our dynamic estimator was also compared with a static estimator and the traditional adaptive filtering method. We observed a significant improvement (two-tailed paired t-test, p < 0.05) in both HbO and HbR recovery using our Kalman filter dynamic estimator compared to the traditional adaptive filter, the static estimator and the standard GLM technique. PMID:21385616

Superior anticancer activity is demonstrated by total extract of Curcuma longa L. as opposed to individual curcuminoids separated by centrifugal partition chromatography.

PubMed

Kukula-Koch, Wirginia; Grabarska, Aneta; Łuszczki, Jarogniew; Czernicka, Lidia; Nowosadzka, Ewa; Gumbarewicz, Ewelina; Jarząb, Agata; Audo, Gregoire; Upadhyay, Shakti; Głowniak, Kazimierz; Stepulak, Andrzej

2018-05-01

Three curcuminoids: bisdemethoxycurcumin, demethoxycurcumin, and curcumin from turmeric were successfully separated by a high capacity solvent system composed of heptane: chloroform: methanol: water mixture (5: 6: 3: 2 v/v/v/v) tailored for centrifugal partition chromatographs at K-values of 0.504, 1.057, 1.644, respectively. These three ferulic acid derivatives obtained at a purity rate exceeding 95% were analysed by an HPLC-MS spectrometer. Turmeric extract inhibited the proliferation/viability of A549 human lung cancer, HT29 colon cancer, and T98G glioblastoma cell lines in (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay (MTT). Single curcuminoids significantly decreased the viability/proliferation of lung cancer cells in a dose-dependent manner. However, total extract displayed the superior anticancer activity in the investigated cell lines. Crude extract in combination with cisplatin augmented the decrease in the viability of cancer cells compared with single compound treatment in A549 lung cancer cells. Total extract of Curcuma longa could be regarded as being more effective against lung cancer cells in vitro than its separated compounds. Copyright © 2018 John Wiley & Sons, Ltd.

Structural phylogenetic analysis of activation-induced deaminase function.

PubMed

Ichikawa, H Travis; Sowden, Mark P; Torelli, Andrew T; Bachl, Jürgen; Huang, Pinwei; Dance, Geoffrey S C; Marr, Shauna H; Robert, Jacques; Wedekind, Joseph E; Smith, Harold C; Bottaro, Andrea

2006-07-01

In mammals, activation-induced deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) of Ig genes. SHM and CSR activities require separate regions within AID. A chromosome region maintenance 1 (CRM1)-dependent nuclear export signal (NES) at the AID C terminus is necessary for CSR, and has been suggested to associate with CSR-specific cofactors. CSR appeared late in AID evolution, during the emergence of land vertebrates from bony fish, which only display SHM. Here, we show that AID from African clawed frog (Xenopus laevis), but not pufferfish (Takifugu rubripes), can induce CSR in AID-deficient mouse B cells, although both are catalytically active in bacteria and mammalian cell systems, albeit at decreased level. Like mammalian AID, Takifugu AID is actively exported from the cell nucleus by CRM1, and the Takifugu NES can substitute for the equivalent region in human AID, indicating that all the CSR-essential NES motif functions evolutionarily predated CSR activity. We also show that fusion of the Takifugu AID catalytic domain to the entire human noncatalytic domain restores activity in mammalian cells, suggesting that AID features mapping within the noncatalytic domain, but outside the NES, influence its function.

Dual-induced multifractality in online viewing activity.

PubMed

Qin, Yu-Hao; Zhao, Zhi-Dan; Cai, Shi-Min; Gao, Liang; Stanley, H Eugene

2018-01-01

Although recent studies have found that the long-term correlations relating to the fat-tailed distribution of inter-event times exist in human activity and that these correlations indicate the presence of fractality, the property of fractality and its origin have not been analyzed. We use both detrended fluctuation analysis and multifractal detrended fluctuation analysis to analyze the time series in online viewing activity separating from Movielens and Netflix. We find long-term correlations at both the individual and communal levels and that the extent of correlation at the individual level is determined by the activity level. These long-term correlations also indicate that there is fractality in the pattern of online viewing. We first find a multifractality that results from the combined effect of the fat-tailed distribution of inter-event times (i.e., the times between successive viewing actions of individuals) and the long-term correlations in online viewing activity and verify this finding using three synthesized series. Therefore, it can be concluded that the multifractality in online viewing activity is caused by both the fat-tailed distribution of inter-event times and the long-term correlations and that this enlarges the generic property of human activity to include not just physical space but also cyberspace.

Dual-induced multifractality in online viewing activity

NASA Astrophysics Data System (ADS)

Qin, Yu-Hao; Zhao, Zhi-Dan; Cai, Shi-Min; Gao, Liang; Stanley, H. Eugene

2018-01-01

Although recent studies have found that the long-term correlations relating to the fat-tailed distribution of inter-event times exist in human activity and that these correlations indicate the presence of fractality, the property of fractality and its origin have not been analyzed. We use both detrended fluctuation analysis and multifractal detrended fluctuation analysis to analyze the time series in online viewing activity separating from Movielens and Netflix. We find long-term correlations at both the individual and communal levels and that the extent of correlation at the individual level is determined by the activity level. These long-term correlations also indicate that there is fractality in the pattern of online viewing. We first find a multifractality that results from the combined effect of the fat-tailed distribution of inter-event times (i.e., the times between successive viewing actions of individuals) and the long-term correlations in online viewing activity and verify this finding using three synthesized series. Therefore, it can be concluded that the multifractality in online viewing activity is caused by both the fat-tailed distribution of inter-event times and the long-term correlations and that this enlarges the generic property of human activity to include not just physical space but also cyberspace.

Two-dimensional zymography differentiates gelatinase isoforms in stimulated microglial cells and in brain tissues of acute brain injuries.

PubMed

Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Tomlinson, Brittany N; Wesley, Jennifer M; Sun, Grace Y; Whaley-Connell, Adam T; Sowers, James R; Cui, Jiankun; Gu, Zezong

2015-01-01

Excessive activation of gelatinases (MMP-2/-9) is a key cause of detrimental outcomes in neurodegenerative diseases. A single-dimension zymography has been widely used to determine gelatinase expression and activity, but this method is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity could be modified at transcriptional and posttranslational levels. In this study, we investigated gelatinase isoforms under in vitro and in vivo conditions using two-dimensional (2D) gelatin zymography electrophoresis, a protocol allowing separation of proteins based on isoelectric points (pI) and molecular weights. We observed organomercuric chemical 4-aminophenylmercuric acetate-induced activation of MMP-2 isoforms with variant pI values in the conditioned medium of human fibrosarcoma HT1080 cells. Studies with murine BV-2 microglial cells indicated a series of proform MMP-9 spots separated by variant pI values due to stimulation with lipopolysaccharide (LPS). The MMP-9 pI values were shifted after treatment with alkaline phosphatase, suggesting presence of phosphorylated isoforms due to the proinflammatory stimulation. Similar MMP-9 isoforms with variant pI values in the same molecular weight were also found in mouse brains after ischemic and traumatic brain injuries. In contrast, there was no detectable pI differentiation of MMP-9 in the brains of chronic Zucker obese rats. These results demonstrated effective use of 2D zymography to separate modified MMP isoforms with variant pI values and to detect posttranslational modifications under different pathological conditions.

Distinct Responses of Stem Cells to Telomere Uncapping-A Potential Strategy to Improve the Safety of Cell Therapy.

PubMed

Liu, Chang Ching; Ma, Dong Liang; Yan, Ting-Dong; Fan, XiuBo; Poon, Zhiyong; Poon, Lai-Fong; Goh, Su-Ann; Rozen, Steve G; Hwang, William Ying Khee; Tergaonkar, Vinay; Tan, Patrick; Ghosh, Sujoy; Virshup, David M; Goh, Eyleen L K; Li, Shang

2016-10-01

In most human somatic cells, the lack of telomerase activity results in progressive telomere shortening during each cell division. Eventually, DNA damage responses triggered by critically short telomeres induce an irreversible cell cycle arrest termed replicative senescence. However, the cellular responses of human pluripotent stem cells to telomere uncapping remain unknown. We generated telomerase knockout human embryonic stem (ES) cells through gene targeting. Telomerase inactivation in ES cells results in progressive telomere shortening. Telomere DNA damage in ES cells and neural progenitor cells induces rapid apoptosis when telomeres are uncapped, in contrast to fibroblast cells that enter a state of replicative senescence. Significantly, telomerase inactivation limits the proliferation capacity of human ES cells without affecting their pluripotency. By targeting telomerase activity, we can functionally separate the two unique properties of human pluripotent stem cells, namely unlimited self-renewal and pluripotency. We show that the potential of ES cells to form teratomas in vivo is dictated by their telomere length. By controlling telomere length of ES cells through telomerase inactivation, we can inhibit teratoma formation and potentially improve the safety of cell therapies involving terminally differentiated cells as well as specific progenitor cells that do not require sustained cellular proliferation in vivo, and thus sustained telomerase activity. Stem Cells 2016;34:2471-2484. © 2016 AlphaMed Press.

Determination and Isolation of Four Anti-tumour Saponins from Lonicera macranthoides by HPLC-ESI-QTOF/MS and HSCCC.

PubMed

Liu, Xuehui; Zhou, Rongrong; Shen, Bingbing; Chen, Lin; Zhou, Qingyijun; Wan, Dan; Huang, Luqi; Zhang, Shuihan

2017-01-01

Lonicera macranthoides is a Chinese herb that contains a large number of bioactive spanions possessing important pharmacological activities, such as anti-tumour activity. However, detailed information about their anti-tumor activity and bioactive compounds is limited. In order to evaluate the scientific basis, the method of high-speed counter-current chromatography (HSCCC) combined with high performance liquid chromatography mass spectrometry (HPLC-ESI-QTOF/MS) has been developed to separate, purify and analyze saponins from Lonicera macranthoides. Four main saponins, Macranthoidin B (I), Macranthoidin A (II), Macranthoides B (III) and Akebia saponin D (IV) were separated by HSCCC with the solvent systems of ethyl acetate-nbutanol- water (3:2:5) and n-butanol-water-methanol-ethyl acetate (1:6:0.5:4). The purities of these four bioactive ingredients (I-IV) identified and detected by HPLC-ESI-QTOF/MS were 95.1%, 92.7%, 91.8% and 96.3%, respectively. The separated saponins were evaluated for their cytotoxic activities against six tumor cell lines (MCF-7, Hela, A549, HepG2, HT29 and Eca109). Results show that compounds I-IV exhibited particular significant anti-tumor activities against human mammary adenocarcinoma MCF-7 cell with IC50 values ranging from 12.7 to 30.8 µM. It was demonstrated that the combinative method using HPLC-ESI-QTOF/MS and HSCCC was suitable for rapid screening and isolating saponins of Lonicera macranthoides and the isolated compounds have great potential for the development of new antitumor drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enhanced protein electrophoresis technique for separating human skeletal muscle myosin heavy chain isoforms

NASA Technical Reports Server (NTRS)

Bamman, M. M.; Clarke, M. S.; Talmadge, R. J.; Feeback, D. L.

1999-01-01

Talmadge and Roy (J. Appl. Physiol. 1993, 75, 2337-2340) previously established a sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) protocol for separating all four rat skeletal muscle myosin heavy chain (MHC) isoforms (MHC I, IIa, IIx, IIb); however, when applied to human muscle, the type II MHC isoforms (Ila, IIx) are not clearly distinguished. In this brief paper we describe a modification of the SDS-PAGE protocol which yields distinct and consistent separation of all three adult human MHC isoforms (MHC I, IIa, IIx) in a minigel system. MHC specificity of each band was confirmed by Western blot using three monoclonal IgG antibodies (mAbs) immunoreactive against MHCI (mAb MHCs, Novacastra Laboratories), MHCI+IIa (mAb BF-35), and MHCIIa+IIx (mAb SC-71). Results provide a valuable SDS-PAGE minigel technique for separating MHC isoforms in human muscle without the difficult task of casting gradient gels.

Evolutionary awareness.

PubMed

Gorelik, Gregory; Shackelford, Todd K

2014-08-27

In this article, we advance the concept of "evolutionary awareness," a metacognitive framework that examines human thought and emotion from a naturalistic, evolutionary perspective. We begin by discussing the evolution and current functioning of the moral foundations on which our framework rests. Next, we discuss the possible applications of such an evolutionarily-informed ethical framework to several domains of human behavior, namely: sexual maturation, mate attraction, intrasexual competition, culture, and the separation between various academic disciplines. Finally, we discuss ways in which an evolutionary awareness can inform our cross-generational activities-which we refer to as "intergenerational extended phenotypes"-by helping us to construct a better future for ourselves, for other sentient beings, and for our environment.

Detailed results of ASTP experiment MA-011. [biological processing facility in space

NASA Technical Reports Server (NTRS)

Seaman, G. V. F.; Allen, R. E.; Barlow, G. H.; Bier, M.

1976-01-01

This experiment was developed in order to conduct engineering and operational tests of electrokinetic equipment in a micro-gravity environment. The experimental hardware in general functioned as planned and electrophoretic separations were obtained in space. The results indicated the development of satisfactory sample collection, return, and preservation techniques. The application of a near-zero zeta potential interior wall coating to the experimental columns, confirmation of biocompatibility of all appropriate hardware components, and use of a sterile operating environment provided a significant step forward in the development of a biological processing facility in space. A separation of a test of aldehyde-fixed rabbit, human, and horse red blood cells was obtained. Human kidney cells were separated into several components and viable cells returned to earth. The isotachophoretic separation of red cells was also demonstrated. Problems associated with the hardware led to a lack of success in the attempt to separate subpopulations of human lymphocytes.

Active and separate secretion of fiber and penton base during the early phase of Ad2 or Ad5 infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Yuhua; Zhang, Bo; Hou, Weihong

Fiber and penton base overproduced in adenovirus (Ad) infected cells can be secreted prior to progeny release and thereby regulate progeny spread. We aimed to investigate the mechanisms of fiber and penton base secretion in Ad2- or Ad5-infected A549 cells. Our flow cytometry analyses detected abundant surface fiber molecules, but little penton base molecules at 12 h post infection. Immunogold staining combined with transmission electron microscopic analyses revealed separate, non-co-localized release of fiber and penton base in the proximity of the plasma membrane. Depolymerization of microtubule and actin cytoskeletons, and inhibition of Rock kinase and myosin II activity together demonstratedmore » cytoskeletal network-dependent fiber secretion. Inhibition of intracellular calcium [Ca{sup 2+}]{sub i} signaling caused diminished fiber secretion, which was associated with diminished progeny production. Thus, fiber and penton base are actively and separately secreted during the early stages of Ad2 or Ad5 infection, their secretion may play important role in Ad life cycle. - Highlights: •Excessive production of structural proteins is common to viral infection, which may regulate the host-virus equilibrium and the spreading of viruses. •The adenovirus (Ad) structural proteins, fiber and penton base, are respectively important for Ad binding to its receptor and subsequent internalization in host cells. In Ad infected cells, these two structural proteins are excessively produced. •The mechanisms underlying the release of fiber and penton base molecules at the early phase of Ad infection is yet poorly understood. •Our studies show that in Ad5 or Ad2 infected A549 cells, fiber and penton base molecules are actively and separately secreted. •Fiber secretion is dependent on cytoskeleton-mediated protein traffic. •Inhibition of myosin II motor and Ca{sup 2+} signaling activity significantly diminishes fiber secretion. •These findings could contribute to our understanding of Ad spread in human populations.« less

Incorporating Human Movement Behavior into the Analysis of Spatially Distributed Infrastructure.

PubMed

Wu, Lihua; Leung, Henry; Jiang, Hao; Zheng, Hong; Ma, Li

2016-01-01

For the first time in human history, the majority of the world's population resides in urban areas. Therefore, city managers are faced with new challenges related to the efficiency, equity and quality of the supply of resources, such as water, food and energy. Infrastructure in a city can be viewed as service points providing resources. These service points function together as a spatially collaborative system to serve an increasing population. To study the spatial collaboration among service points, we propose a shared network according to human's collective movement and resource usage based on data usage detail records (UDRs) from the cellular network in a city in western China. This network is shown to be not scale-free, but exhibits an interesting triangular property governed by two types of nodes with very different link patterns. Surprisingly, this feature is consistent with the urban-rural dualistic context of the city. Another feature of the shared network is that it consists of several spatially separated communities that characterize local people's active zones but do not completely overlap with administrative areas. According to these features, we propose the incorporation of human movement into infrastructure classification. The presence of well-defined spatially separated clusters confirms the effectiveness of this approach. In this paper, our findings reveal the spatial structure inside a city, and the proposed approach provides a new perspective on integrating human movement into the study of a spatially distributed system.

Human skin based triboelectric nanogenerators for harvesting biomechanical energy and as self-powered active tactile sensor system.

PubMed

Yang, Ya; Zhang, Hulin; Lin, Zong-Hong; Zhou, Yu Sheng; Jing, Qingshen; Su, Yuanjie; Yang, Jin; Chen, Jun; Hu, Chenguo; Wang, Zhong Lin

2013-10-22

We report human skin based triboelectric nanogenerators (TENG) that can either harvest biomechanical energy or be utilized as a self-powered tactile sensor system for touch pad technology. We constructed a TENG utilizing the contact/separation between an area of human skin and a polydimethylsiloxane (PDMS) film with a surface of micropyramid structures, which was attached to an ITO electrode that was grounded across a loading resistor. The fabricated TENG delivers an open-circuit voltage up to -1000 V, a short-circuit current density of 8 mA/m(2), and a power density of 500 mW/m(2) on a load of 100 MΩ, which can be used to directly drive tens of green light-emitting diodes. The working mechanism of the TENG is based on the charge transfer between the ITO electrode and ground via modulating the separation distance between the tribo-charged skin patch and PDMS film. Furthermore, the TENG has been used in designing an independently addressed matrix for tracking the location and pressure of human touch. The fabricated matrix has demonstrated its self-powered and high-resolution tactile sensing capabilities by recording the output voltage signals as a mapping figure, where the detection sensitivity of the pressure is about 0.29 ± 0.02 V/kPa and each pixel can have a size of 3 mm × 3 mm. The TENGs may have potential applications in human-machine interfacing, micro/nano-electromechanical systems, and touch pad technology.

Terminal Area Productivity Program: Dynamic Spacing Human Factors

NASA Technical Reports Server (NTRS)

Kanki, Barbara G.

1997-01-01

Dynamic spacing human factors deals with the following human factors issues: define controller limits to incorporating dynamic changes in separation standards; identify timing, planning, and coordination strategies; and consider consistency with current practices, policies, and regulations. The AVOSS technologies will make it possible to reduce separation standards in the terminal area under certain meteorological conditions. This paper contains the following sections: Dynamic space human factors overview, Preliminary tests, and current research status & plans.

The Value of Humans in the Biological Exploration of Space

NASA Astrophysics Data System (ADS)

Cockell, C. S.

2004-06-01

Regardless of the discovery of life on Mars, or of "no apparent life" on Mars, the questions that follow will provide a rich future for biological exploration. Extraordinary pattern recognition skills, decadal assimilation of data and experience, and rapid sample acquisition are just three of the characteristics that make humans the best means we have to explore the biological potential of Mars and other planetary surfaces. I make the case that instead of seeing robots as in conflict, or even in support, of human exploration activity, from the point of view of scientific data gathering and analysis, we should view humans as the most powerful robots we have, thus removing the separation that dogs discussions on the exploration of space. The narrow environmental requirements of humans, although imposing constraints on the life support systems required, is more than compensated for by their capabilities in biological exploration. I support this view with an example of the "Christmas present effect," a simple demonstration of human data and pattern recognition capabilities.

Traveling Theta Waves in the Human Hippocampus

PubMed Central

Zhang, Honghui

2015-01-01

The hippocampal theta oscillation is strongly correlated with behaviors such as memory and spatial navigation, but we do not understand its specific functional role. One hint of theta's function came from the discovery in rodents that theta oscillations are traveling waves that allow parts of the hippocampus to simultaneously exhibit separate oscillatory phases. Because hippocampal theta oscillations in humans have different properties compared with rodents, we examined these signals directly using multielectrode recordings from neurosurgical patients. Our findings confirm that human hippocampal theta oscillations are traveling waves, but also show that these oscillations appear at a broader range of frequencies compared with rodents. Human traveling waves showed a distinctive pattern of spatial propagation such that there is a consistent phase spread across the hippocampus regardless of the oscillations' frequency. This suggests that traveling theta oscillations are important functionally in humans because they coordinate phase coding throughout the hippocampus in a consistent manner. SIGNIFICANCE STATEMENT We show for the first time in humans that hippocampal theta oscillations are traveling waves, moving along the length of the hippocampus in a posterior–anterior direction. The existence of these traveling theta waves is important for understanding hippocampal neural coding because they cause neurons at separate positions in the hippocampus to experience different theta phases simultaneously. The theta phase that a neuron measures is a key factor in how that cell represents behavioral information. Therefore, the existence of traveling theta waves indicates that, to fully understand how a hippocampal neuron represents information, it is vital to also account for that cell's location in addition to conventional measures of neural activity. PMID:26354915

The human gastrin precursor. Characterization of phosphorylated forms and fragments.

PubMed Central

Varro, A; Desmond, H; Pauwels, S; Gregory, H; Young, J; Dockray, G J

1988-01-01

There is a potential phosphorylation site in the C-terminal region of the precursor for the acid-stimulating hormone gastrin, which is immediately adjacent to an important cleavage point. In the present study we have sought to identify, separate, quantify and characterize phosphorylated and unphosphorylated forms of human progastrin and its fragments. Identification was made by two radioimmunoassays: (a) a novel assay employing an antibody raised to intact human progastrin; and (b) an assay using antibody reacting with the C-terminal tryptic fragment of human progastrin, as well as progastrin itself. Two forms of human progastrin isolated from a gastrinoma were separated by ion-exchange h.p.l.c., and had similar elution positions on reverse-phase h.p.l.c. and on gel filtration. The more acidic peptide contained close to equimolar amounts of phosphate. On trypsinization, peptides were released that co-eluted on ion-exchange h.p.l.c. with, and had the immunochemical properties of, naturally occurring C-terminal fragments of progastrin. One of the latter was isolated and shown by Edman degradation after derivatization with ethanethiol to have the sequence Ser (P)-Ala-Glu-Asp-Glu-Asn. Similar peptides occur in antral mucosa resected from ulcer patients. The unphosphorylated forms of progastrin predominated, whereas the phosphorylated forms of the C-terminal fragments were predominant. This distribution could be explained by preferential cleavage of phosphorylated progastrin. We conclude that in human progastrin, Ser-96 can occur in the phosphorylated form; this residue immediately follows a pair of basic residues (Arg-Arg) that are cleaved during synthesis of the biologically active product. PMID:3223964

Electrophoretic cell separation by means of immunomicrospheres

NASA Technical Reports Server (NTRS)

Rembaum, A.; Smolka, A. J. K.

1980-01-01

The electrophoretic mobility of fixed human red blood cells immunologically labeled with polymeric (4-vinyl)pyridine or polyglutaraldehyde microspheres was altered to a considerable extent. This observation was utilized in the preparative scale electrophoretic separation of human and turkey fixed red blood cells, whose mobilities under normal physiological conditions do not differ sufficiently to allow their separation by continuous flow electrophoresis. It is suggested that resolution in the electrophoretic separation of cell subpopulations, currently limited by finite and often overlapping mobility distributions, may be significantly enhanced by immuno-specific labeling of target populations using microspheres.

EEG Oscillations Are Modulated in Different Behavior-Related Networks during Rhythmic Finger Movements.

PubMed

Seeber, Martin; Scherer, Reinhold; Müller-Putz, Gernot R

2016-11-16

Sequencing and timing of body movements are essential to perform motoric tasks. In this study, we investigate the temporal relation between cortical oscillations and human motor behavior (i.e., rhythmic finger movements). High-density EEG recordings were used for source imaging based on individual anatomy. We separated sustained and movement phase-related EEG source amplitudes based on the actual finger movements recorded by a data glove. Sustained amplitude modulations in the contralateral hand area show decrease for α (10-12 Hz) and β (18-24 Hz), but increase for high γ (60-80 Hz) frequencies during the entire movement period. Additionally, we found movement phase-related amplitudes, which resembled the flexion and extension sequence of the fingers. Especially for faster movement cadences, movement phase-related amplitudes included high β (24-30 Hz) frequencies in prefrontal areas. Interestingly, the spectral profiles and source patterns of movement phase-related amplitudes differed from sustained activities, suggesting that they represent different frequency-specific large-scale networks. First, networks were signified by the sustained element, which statically modulate their synchrony levels during continuous movements. These networks may upregulate neuronal excitability in brain regions specific to the limb, in this study the right hand area. Second, movement phase-related networks, which modulate their synchrony in relation to the movement sequence. We suggest that these frequency-specific networks are associated with distinct functions, including top-down control, sensorimotor prediction, and integration. The separation of different large-scale networks, we applied in this work, improves the interpretation of EEG sources in relation to human motor behavior. EEG recordings provide high temporal resolution suitable to relate cortical oscillations to actual movements. Investigating EEG sources during rhythmic finger movements, we distinguish sustained from movement phase-related amplitude modulations. We separate these two EEG source elements motivated by our previous findings in gait. Here, we found two types of large-scale networks, representing the right fingers in distinction from the time sequence of the movements. These findings suggest that EEG source amplitudes reconstructed in a cortical patch are the superposition of these simultaneously present network activities. Separating these frequency-specific networks is relevant for studying function and possible dysfunction of the cortical sensorimotor system in humans as well as to provide more advanced features for brain-computer interfaces. Copyright © 2016 the authors 0270-6474/16/3611671-11$15.00/0.

Redox‐Active Separators for Lithium‐Ion Batteries

PubMed Central

Pan, Ruijun; Ruan, Changqing; Edström, Kristina; Strømme, Maria

2017-01-01

Abstract A bilayered cellulose‐based separator design is presented that can enhance the electrochemical performance of lithium‐ion batteries (LIBs) via the inclusion of a porous redox‐active layer. The proposed flexible redox‐active separator consists of a mesoporous, insulating nanocellulose fiber layer that provides the necessary insulation between the electrodes and a porous, conductive, and redox‐active polypyrrole‐nanocellulose layer. The latter layer provides mechanical support to the nanocellulose layer and adds extra capacity to the LIBs. The redox‐active separator is mechanically flexible, and no internal short circuits are observed during the operation of the LIBs, even when the redox‐active layer is in direct contact with both electrodes in a symmetric lithium–lithium cell. By replacing a conventional polyethylene separator with a redox‐active separator, the capacity of the proof‐of‐concept LIB battery containing a LiFePO4 cathode and a Li metal anode can be increased from 0.16 to 0.276 mA h due to the capacity contribution from the redox‐active separator. As the presented redox‐active separator concept can be used to increase the capacities of electrochemical energy storage systems, this approach may pave the way for new types of functional separators. PMID:29593967

Redox-Active Separators for Lithium-Ion Batteries.

PubMed

Wang, Zhaohui; Pan, Ruijun; Ruan, Changqing; Edström, Kristina; Strømme, Maria; Nyholm, Leif

2018-03-01

A bilayered cellulose-based separator design is presented that can enhance the electrochemical performance of lithium-ion batteries (LIBs) via the inclusion of a porous redox-active layer. The proposed flexible redox-active separator consists of a mesoporous, insulating nanocellulose fiber layer that provides the necessary insulation between the electrodes and a porous, conductive, and redox-active polypyrrole-nanocellulose layer. The latter layer provides mechanical support to the nanocellulose layer and adds extra capacity to the LIBs. The redox-active separator is mechanically flexible, and no internal short circuits are observed during the operation of the LIBs, even when the redox-active layer is in direct contact with both electrodes in a symmetric lithium-lithium cell. By replacing a conventional polyethylene separator with a redox-active separator, the capacity of the proof-of-concept LIB battery containing a LiFePO 4 cathode and a Li metal anode can be increased from 0.16 to 0.276 mA h due to the capacity contribution from the redox-active separator. As the presented redox-active separator concept can be used to increase the capacities of electrochemical energy storage systems, this approach may pave the way for new types of functional separators.

Mutational analysis of the reverse transcriptase and ribonuclease H domains of the human foamy virus.

PubMed Central

Kögel, D; Aboud, M; Flügel, R M

1995-01-01

Human foamy or spuma virus (HFV) codes for a distinct set of pol gen products. To determine the minimal requirements for the HFV enzymatic activities, defined residues of the reverse transcriptase (RT) and ribo-nuclease H (RNase H) domain of the HFV pol gene were mutated by site-specific PCR mutagenesis. The mutant gene products were bacterially expressed, purified by Ni2+ chelate affinity chromatography and characterised by Western blotting. The enzymatic activities of the individual recombinant HFV pol mutant proteins were characterised by the situ RT, RNase H and RNase H assays. Two substitution mutants reached RT activity levels higher than that of the intact recombinant HFV RT-RH-His. When the catalytically essential D508 was substituted by A508, 5% of RNase H activity was retained while DNA polymerase activity increased 2-fold. A deletion of 11 amino acid residues in the hinge region completely abolished DNA polymerase while RNase H activity decreased 2-fold. A deletion mutant in the C-terminal RH domain showed no RNase H but retained RNase H activity indicating that the activities are genetically separable. The combined data reveal that the HFV DNA polymerase and RNase H activities are interdependent. Images PMID:7544460

A combined A431 cell membrane chromatography and online high performance liquid chromatography/mass spectrometry method for screening compounds from total alkaloid of Radix Caulophylli acting on the human EGFR.

PubMed

Sun, Meng; Ren, Jing; Du, Hui; Zhang, Yanmin; Zhang, Jie; Wang, Sicen; He, Langchong

2010-10-15

We have developed an online analytical method that combines A431 cell membrane chromatography (A431/CMC) with high performance liquid chromatography and mass spectrometry (LC/MS) for identifying active components from Radix Caulophylli acting on human EGFR. Retention fractions on A431/CMC model were captured onto an enrichment column and the components were directly analyzed by combining a 10-port column switcher with an LC/MS system for separation and preliminary identification. Using Sorafenib tosylate as a positive control, taspine and caulophine from Radix Caulophylli were identified as the active molecules which could act on the EGFR. This A431/CMC-online-LC/MS method can be applied for screening active components acting on EGFR from traditional Chinese medicines exemplified by Radix Caulophylli and will be of great utility in drug discovery using natural medicinal herbs as a source of novel compounds. Copyright © 2010 Elsevier B.V. All rights reserved.

Activity-based mass spectrometric characterization of proteases and inhibitors in human saliva

PubMed Central

Sun, Xiuli; Salih, Erdjan; Oppenheim, Frank G.; Helmerhorst, Eva J.

2009-01-01

Proteases present in oral fluid effectively modulate the structure and function of some salivary proteins and have been implicated in tissue destruction in oral disease. To identify the proteases operating in the oral environment, proteins in pooled whole saliva supernatant were separated by anion-exchange chromatography and individual fractions were analyzed for proteolytic activity by zymography using salivary histatins as the enzyme substrates. Protein bands displaying proteolytic activity were particularly prominent in the 50–75 kDa region. Individual bands were excised, in-gel trypsinized and subjected to LC/ESI-MS/MS. The data obtained were searched against human, oral microbial and protease databases. A total of 13 proteases were identified all of which were of mammalian origin. Proteases detected in multiple fractions with cleavage specificities toward arginine and lysine residues, were lactotransferrin, kallikrein-1, and human airway trypsin-like protease. Unexpectedly, ten protease inhibitors were co-identified suggesting they were associated with the proteases in the same fractions. The inhibitors found most frequently were alpha-2-macroglobulin-like protein 1, alpha-1-antitrypsin, and leukocyte elastase inhibitor. Regulation of oral fluid proteolysis is highly important given that an inbalance in such activities has been correlated to a variety of pathological conditions including oral cancer. PMID:20011683

Comparative study on digestive lipase activities on the self emulsifying excipient Labrasol, medium chain glycerides and PEG esters.

PubMed

Fernandez, Sylvie; Jannin, Vincent; Rodier, Jean-David; Ritter, Nicolas; Mahler, Bruno; Carrière, Frédéric

2007-05-01

Labrasol is a lipid-based self-emulsifying excipient used in the preparation of lipophilic drugs intended for oral delivery. It is mainly composed of PEG esters and glycerides with medium acyl chains, which are potential substrates for digestive lipases. The hydrolysis of Labrasol by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases was investigated in the present study. Classical human pancreatic lipase (HPL) and porcine pancreatic lipase, which are the main lipases involved in the digestion of dietary triglycerides, showed very low levels of activity on the entire Labrasol excipient as well as on separated fractions of glycerides and PEG esters. On the other hand, gastric lipase, pancreatic lipase-related protein 2 (PLRP2) and carboxyl ester hydrolase (CEH) showed high specific activities on Labrasol. These lipases were found to hydrolyze the main components of Labrasol (PEG esters and monoglycerides) used as individual substrates, whereas these esters were found to be poor substrates for HPL. The lipolytic activity of pancreatic extracts and human pancreatic juice on Labrasol(R) is therefore mainly due to the combined action of CEH and PLRP2. These two pancreatic enzymes, together with gastric lipase, are probably the main enzymes involved in the in vivo lipolysis of Labrasol taken orally.

Inhibition of carboxylesterase activity of THP1 monocytes/macrophages and recombinant human carboxylesterase 1 by oxysterols and fatty acids

PubMed Central

Crow, J. Allen; Herring, Katye L.; Xie, Shuqi; Borazjani, Abdolsamad; Potter, Philip M.; Ross, Matthew K.

2009-01-01

Summary Two major isoforms of human carboxylesterases (CEs) are found in metabolically active tissues, CES1 and CES2. These hydrolytic enzymes are involved in xenobiotic and endobiotic metabolism. CES1 is abundantly expressed in human liver and monocytes/macrophages, including the THP1 cell line; CES2 is expressed in liver but not in monocytes/macrophages. The cholesteryl ester hydrolysis activity in human macrophages has been attributed to CES1. Here, we report the direct inhibitory effects of several endogenous oxysterols and fatty acids on the CE activity of THP1 monocytes/macrophages and recombinant human CES1 and CES2. Using THP1 whole-cell lysates we found: (1) 27-hydroxycholesterol (27-HC) is a potent inhibitor of carboxylesterase activity (IC50=33 nM); (2) 24(S),25-epoxycholesterol had moderate inhibitory activity (IC50=8.1 μM); and (3) cholesterol, 7-ketocholesterol, 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, and 25-hydroxycholesterol each had little inhibitory activity. 27-HC was a partially noncompetitive inhibitor of recombinant CES1 (Kiapp=10 nM) and impaired intracellular CES1 activity following treatment of intact THP1 cells. In contrast, recombinant CES2 activity was not inhibited by 27-HC, suggesting isoform-selective inhibition by 27-HC. Furthermore, unsaturated fatty acids were better inhibitors of CES1 activity than saturated fatty acids, while CES2 activity was unaffected by any fatty acid. Arachidonic acid (AA) was the most potent fatty acid inhibitor of recombinant CES1 and acted by a noncompetitive mechanism (Kiapp=1.7 μM); when not complexed to albumin, exogenous AA penetrated intact THP1 cells and inhibited CES1. Inhibition results are discussed in light of recent structural models for CES1 that describe ligand binding sites separate from the active site. In addition, oxysterol-mediated inhibition of CES1 activity was demonstrated by pretreatment of human liver homogenates or intact THP1 cells with exogenous 27-HC, which resulted in significantly reduced hydrolysis of the pyrethroid insecticide bioresmethrin, a CES1-specific xenobiotic substrate. Collectively, these findings suggest that CE activity of recombinant CES1, cell lysates, and intact cells can be impaired by naturally occurring lipids, which may compromise the ability of CES1 to both detoxify environmental pollutants and metabolize endogenous compounds in vivo. PMID:19761868

Baselines and Degradation of Coral Reefs in the Northern Line Islands

PubMed Central

Sandin, Stuart A.; Smith, Jennifer E.; DeMartini, Edward E.; Dinsdale, Elizabeth A.; Donner, Simon D.; Friedlander, Alan M.; Konotchick, Talina; Malay, Machel; Maragos, James E.; Obura, David; Pantos, Olga; Paulay, Gustav; Richie, Morgan; Rohwer, Forest; Schroeder, Robert E.; Walsh, Sheila; Jackson, Jeremy B. C.; Knowlton, Nancy; Sala, Enric

2008-01-01

Effective conservation requires rigorous baselines of pristine conditions to assess the impacts of human activities and to evaluate the efficacy of management. Most coral reefs are moderately to severely degraded by local human activities such as fishing and pollution as well as global change, hence it is difficult to separate local from global effects. To this end, we surveyed coral reefs on uninhabited atolls in the northern Line Islands to provide a baseline of reef community structure, and on increasingly populated atolls to document changes associated with human activities. We found that top predators and reef-building organisms dominated unpopulated Kingman and Palmyra, while small planktivorous fishes and fleshy algae dominated the populated atolls of Tabuaeran and Kiritimati. Sharks and other top predators overwhelmed the fish assemblages on Kingman and Palmyra so that the biomass pyramid was inverted (top-heavy). In contrast, the biomass pyramid at Tabuaeran and Kiritimati exhibited the typical bottom-heavy pattern. Reefs without people exhibited less coral disease and greater coral recruitment relative to more inhabited reefs. Thus, protection from overfishing and pollution appears to increase the resilience of reef ecosystems to the effects of global warming. PMID:18301734

Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks

PubMed Central

Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

2015-01-01

Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention. PMID:25745395

Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks.

PubMed

Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

2015-01-01

Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention.

Topical application of RTA 408 lotion activates Nrf2 in human skin and is well-tolerated by healthy human volunteers.

PubMed

Reisman, Scott A; Goldsberry, Angela R; Lee, Chun-Yue I; O'Grady, Megan L; Proksch, Joel W; Ward, Keith W; Meyer, Colin J

2015-07-14

Topical application of the synthetic triterpenoid RTA 408 to rodents elicits a potent dermal cytoprotective phenotype through activation of the transcription factor Nrf2. Therefore, studies were conducted to investigate if such cytoprotective properties translate to human dermal cells, and a topical lotion formulation was developed and evaluated clinically. In vitro, RTA 408 (3-1000 nM) was incubated with primary human keratinocytes for 16 h. Ex vivo, RTA 408 (0.03, 0.3, or 3 %) was applied to healthy human skin explants twice daily for 3 days. A Phase 1 healthy volunteer clinical study with RTA 408 Lotion (NCT02029716) consisted of 3 sequential parts. In Part A, RTA 408 Lotion (0.5 %, 1 %, and 3 %) and lotion vehicle were applied to individual 4-cm(2) sites twice daily for 14 days. In Parts B and C, separate groups of subjects had 3 % RTA 408 Lotion applied twice daily to a 100-cm(2) site for 14 days or a 500-cm(2) site for 28 days. RTA 408 was well-tolerated in both in vitro and ex vivo settings up to the highest concentrations tested. Further, RTA 408 significantly and dose-dependently induced a variety of Nrf2 target genes. Clinically, RTA 408 Lotion was also well-tolerated up to the highest concentration, largest surface area, and longest duration tested. Moreover, significant increases in expression of the prototypical Nrf2 target gene NQO1 were observed in skin biopsies, suggesting robust activation of the pharmacological target. Overall, these data suggest RTA 408 Lotion is well-tolerated, activates Nrf2 in human skin, and appears suitable for continued clinical development.

Production of human insulin in an E. coli system with Met-Lys-human proinsulin as the expressed precursor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin-Qiu Chen; Hong-Tao Zhang; Mei-Hao Hu

1995-10-01

The construction of a gene encoding Lys-human proinsulin, its direct expression in E.coli, and the simple purification procedure are described here. The temperature inducible promotor was employed for induction in a very short time. The expression level could reach 20-30%. After a simple downstream processing and only one step of Sephadex G50 purification, 150 mg recombinant Lys-human proinsulin with a purity of up to 90% could be obtained easily from 1 L of high density fermentation medium. The obtained product is in the form of Met-Lys-human proinsulin because of the failure of the bacterial host to remove the initiator methioninemore » residue. The Lys-human proinsulin could be changed into human insulin by tryspin and carboxypeptidase B treatment in later steps. After separation with DEAE Sephadex A25, human insulin with expected amino acid composition and full native biological activity could be obtained with a yield of 50 mg/L fermentation medium. 20 refs., 5 figs., 4 tabs.« less

Childhood separation experience predicts HPA axis hormonal responses in late adulthood: a natural experiment of World War II.

PubMed

Pesonen, Anu-Katriina; Räikkönen, Katri; Feldt, Kimmo; Heinonen, Kati; Osmond, Clive; Phillips, David I W; Barker, David J P; Eriksson, Johan G; Kajantie, Eero

2010-06-01

Animal models have linked early maternal separation with lifelong changes in hypothalamic-pituitary-adrenocortical (HPA) axis activity. Although this is paralleled in human studies, this is often in the context of other life adversities, for example, divorce or adoption, and it is not known whether early separation in the absence of these factors has long term effects on the HPA axis. The Finnish experience in World War II created a natural experiment to test whether separation from a father serving in the armed forces or from both parents due to war evacuation are associated with alterations in HPA axis response to psychosocial stress in late adulthood. 282 subjects (M=63.5 years, SD=2.5), of whom 85 were non-separated, 129 were separated from their father, and 68 were separated from both their caregivers during WWII, were enlisted to participate in a Trier Social Stress Test (TSST), during which we measured salivary cortisol and, for 215 individuals, plasma cortisol and ACTH concentrations. We used mixed models to study whether parental separation is associated with salivary and plasma cortisol or plasma ACTH reactivity, and linear regressions to analyse differences in the baseline, or incremental area under the cortisol or ACTH curves. Participants separated from their father did not differ significantly from non-separated participants. However, those separated from both parents had higher average salivary cortisol and plasma ACTH concentrations across all time points compared to the non-separated group. They also had higher salivary cortisol reactivity to the TSST. Separated women had higher baselines in plasma cortisol and ACTH, whereas men had higher reactivity in response to stress during the TSST. Participants who had experienced the separation in early childhood were more affected than children separated during infancy or school age. Separation from parents during childhood may alter an individual's stress physiology much later in adult life. Copyright 2009 Elsevier Ltd. All rights reserved.

Storage of Unfed and Leftover Pasteurized Human Milk.

PubMed

Meng, Ting; Perrin, Maryanne T; Allen, Jonathan C; Osborne, Jason; Jones, Frances; Fogleman, April D

2016-12-01

To determine the impact of storage on bacterial growth and immunological activity of pasteurized human milk and leftover pasteurized human milk that has been exposed to the microflora in an infant's mouth. Eighteen mother-infant dyads participated in two separate studies. Mother's milk was pasteurized, and each baby was fed 1 to 2 ounces. Pasteurized and leftover pasteurized milk were stored at room (24°C) and refrigerated temperatures (4°C). After storage, milk was analyzed for bacteria, total protein, lysozyme activity, and secretory immunoglobulin A (SIgA) activity. In pasteurized and leftover pasteurized milk stored in the refrigerator for 7 days, total aerobic bacteria do not increase significantly and total protein and bioactive proteins are stable. At room temperature, there is a significant increase in total aerobic bacteria in leftover pasteurized milk during 12 hours of storage (p < 0.01) and a significant decrease in total protein and SIgA activity in pasteurized milk during 12 hours of storage (p = 0.02 and p = 0.03, respectively). When stored in the refrigerator, pasteurized and leftover pasteurized milk may be stored for at least 7 days when considering the variables studied. Caution should be used when storing pasteurized and leftover pasteurized milk at room temperature to prevent an increase in bacterial growth and a decrease in total protein and SIgA activity.

Synchronization of Human Autonomic Nervous System Rhythms with Geomagnetic Activity in Human Subjects

PubMed Central

McCraty, Rollin; Atkinson, Mike; Stolc, Viktor; Alabdulgader, Abdullah A.; Vainoras, Alfonsas

2017-01-01

A coupling between geomagnetic activity and the human nervous system’s function was identified by virtue of continuous monitoring of heart rate variability (HRV) and the time-varying geomagnetic field over a 31-day period in a group of 10 individuals who went about their normal day-to-day lives. A time series correlation analysis identified a response of the group’s autonomic nervous systems to various dynamic changes in the solar, cosmic ray, and ambient magnetic field. Correlation coefficients and p values were calculated between the HRV variables and environmental measures during three distinct time periods of environmental activity. There were significant correlations between the group’s HRV and solar wind speed, Kp, Ap, solar radio flux, cosmic ray counts, Schumann resonance power, and the total variations in the magnetic field. In addition, the time series data were time synchronized and normalized, after which all circadian rhythms were removed. It was found that the participants’ HRV rhythms synchronized across the 31-day period at a period of approximately 2.5 days, even though all participants were in separate locations. Overall, this suggests that daily autonomic nervous system activity not only responds to changes in solar and geomagnetic activity, but is synchronized with the time-varying magnetic fields associated with geomagnetic field-line resonances and Schumann resonances. PMID:28703754

Activity recognition from minimal distinguishing subsequence mining

NASA Astrophysics Data System (ADS)

Iqbal, Mohammad; Pao, Hsing-Kuo

2017-08-01

Human activity recognition is one of the most important research topics in the era of Internet of Things. To separate different activities given sensory data, we utilize a Minimal Distinguishing Subsequence (MDS) mining approach to efficiently find distinguishing patterns among different activities. We first transform the sensory data into a series of sensor triggering events and operate the MDS mining procedure afterwards. The gap constraints are also considered in the MDS mining. Given the multi-class nature of most activity recognition tasks, we modify the MDS mining approach from a binary case to a multi-class one to fit the need for multiple activity recognition. We also study how to select the best parameter set including the minimal and the maximal support thresholds in finding the MDSs for effective activity recognition. Overall, the prediction accuracy is 86.59% on the van Kasteren dataset which consists of four different activities for recognition.

Task-space separation principle: a force-field approach to motion planning for redundant manipulators.

PubMed

Tommasino, Paolo; Campolo, Domenico

2017-02-03

In this work, we address human-like motor planning in redundant manipulators. Specifically, we want to capture postural synergies such as Donders' law, experimentally observed in humans during kinematically redundant tasks, and infer a minimal set of parameters to implement similar postural synergies in a kinematic model. For the model itself, although the focus of this paper is to solve redundancy by implementing postural strategies derived from experimental data, we also want to ensure that such postural control strategies do not interfere with other possible forms of motion control (in the task-space), i.e. solving the posture/movement problem. The redundancy problem is framed as a constrained optimization problem, traditionally solved via the method of Lagrange multipliers. The posture/movement problem can be tackled via the separation principle which, derived from experimental evidence, posits that the brain processes static torques (i.e. posture-dependent, such as gravitational torques) separately from dynamic torques (i.e. velocity-dependent). The separation principle has traditionally been applied at a joint torque level. Our main contribution is to apply the separation principle to Lagrange multipliers, which act as task-space force fields, leading to a task-space separation principle. In this way, we can separate postural control (implementing Donders' law) from various types of tasks-space movement planners. As an example, the proposed framework is applied to the (redundant) task of pointing with the human wrist. Nonlinear inverse optimization (NIO) is used to fit the model parameters and to capture motor strategies displayed by six human subjects during pointing tasks. The novelty of our NIO approach is that (i) the fitted motor strategy, rather than raw data, is used to filter and down-sample human behaviours; (ii) our framework is used to efficiently simulate model behaviour iteratively, until it converges towards the experimental human strategies.

Analysis and separation of residues important for the chemoattractant and antimicrobial activities of beta-defensin 3.

PubMed

Taylor, Karen; Clarke, David J; McCullough, Bryan; Chin, Wutharath; Seo, Emily; Yang, De; Oppenheim, Joost; Uhrin, Dusan; Govan, John R W; Campopiano, Dominic J; MacMillan, Derek; Barran, Perdita; Dorin, Julia R

2008-03-14

beta-Defensins are important in mammalian immunity displaying both antimicrobial and chemoattractant activities. Three canonical disulfide intramolecular bonds are believed to be dispensable for antimicrobial activity but essential for chemoattractant ability. However, here we show that HBD3 (human beta-defensin 3) alkylated with iodoactemide and devoid of any disulfide bonds is still a potent chemoattractant. Furthermore, when the canonical six cysteine residues are replaced with alanine, the peptide is no longer active as a chemoattractant. These findings are replicated by the murine ortholog Defb14. We restore the chemoattractant activity of Defb14 and HBD3 by introduction of a single cysteine in the fifth position (Cys V) of the beta-defensin six cysteine motif. In contrast, a peptide with a single cysteine at the first position (Cys I) is inactive. Moreover, a range of overlapping linear fragments of Defb14 do not act as chemoattractants, suggesting that the chemotactic activity of this peptide is not dependent solely on an epitope surrounding Cys V. Full-length peptides either with alkylated cysteine residues or with cysteine residues replaced with alanine are still strongly antimicrobial. Defb14 peptide fragments were also tested for antimicrobial activity, and peptides derived from the N-terminal region display potent antimicrobial activity. Thus, the chemoattractant and antimicrobial activities of beta-defensins can be separated, and both of these functions are independent of intramolecular disulfide bonds. These findings are important for further understanding of the mechanism of action of defensins and for therapeutic design.

Initial evaluation of a convection counter streaming galvanization technique of sex separation of human spermatozoa.

PubMed

Daniell, J F; Herbert, C M; Repp, J; Torbit, C A; Wentz, A C

1982-08-01

A new method for separating X and Y human spermatozoa called convection counter streaming galvanization was evaluated. The method was independently performed by this semenology laboratory with the use of the special separation equipment and extending media provided by its developer, Dr. Bhairab C. Bhattacharya. The mean number of Y spermatozoa increased from 48% to 77% in the separated fraction predicted to be Y-enriched. The fraction predicted to be X-enriched increased from a mean of 52% to 77%. The one separation process allowed accumulation of both enriched fractions simultaneously. The separated portions of spermatozoa maintained good motility and penetration of cervical mucus but produced a mean recovery concentration in the X- and Y-enriched fractions of only 15% to 16% of the preseparation concentration.

Elastin-like polypeptides: Therapeutic applications for an emerging class of nanomedicines.

PubMed

Despanie, Jordan; Dhandhukia, Jugal P; Hamm-Alvarez, Sarah F; MacKay, J Andrew

2016-10-28

Elastin-like polypeptides (ELPs) constitute a genetically engineered class of 'protein polymers' derived from human tropoelastin. They exhibit a reversible phase separation whereby samples remain soluble below a transition temperature (T t ) but form amorphous coacervates above T t . Their phase behavior has many possible applications in purification, sensing, activation, and nanoassembly. As humanized polypeptides, they are non-immunogenic, substrates for proteolytic biodegradation, and can be decorated with pharmacologically active peptides, proteins, and small molecules. Recombinant synthesis additionally allows precise control over ELP architecture and molecular weight, resulting in protein polymers with uniform physicochemical properties suited to the design of multifunctional biologics. As such, ELPs have been employed for various uses including as anti-cancer agents, ocular drug delivery vehicles, and protein trafficking modulators. This review aims to offer the reader a catalogue of ELPs, their various applications, and potential for commercialization across a broad spectrum of fields. Copyright © 2015. Published by Elsevier B.V.

Viscoelasticity and plasticity mechanisms of human dentin

NASA Astrophysics Data System (ADS)

Borodin, E. N.; Seyedkavoosi, S.; Zaitsev, D.; Drach, B.; Mikaelyan, K. N.; Panfilov, P. E.; Gutkin, M. Yu.; Sevostianov, I.

2018-01-01

Theoretical models of viscoelastic behavior and plastic deformation mechanisms of human dentin are considered. Using the linear viscoelasticity theory in which creep and relaxation kernels have the form of fraction-exponential functions, numerical values of instantaneous and long-time Young's moduli and other characteristics of dentin viscoelasticity under uniaxial compression are found. As dentin plastic deformation mechanisms, mutual collagen fiber sliding in the region of contact of their side surfaces, separation of these fibers from each other, and irreversible tension of some collagen fibers, are proposed. It is shown that the second mechanism activation requires a smaller stress than that for activating others. The models of plastic zones at the mode I crack tip, which correspond to these mechanisms, are studied. It is shown that the plastic zone size can increase from a few hundreds of nanometers to hundreds of micrometers with increasing applied stress.

Tonic and Rhythmic Spinal Activity Underlying Locomotion.

PubMed

Ivanenko, Yury P; Gurfinkel, Victor S; Selionov, Victor A; Solopova, Irina A; Sylos-Labini, Francesca; Guertin, Pierre A; Lacquaniti, Francesco

2017-05-12

In recent years, many researches put significant efforts into understanding and assessing the functional state of the spinal locomotor circuits in humans. Various techniques have been developed to stimulate the spinal cord circuitries, which may include both diffuse and quite specific tuning effects. Overall, the findings indicate that tonic and rhythmic spinal activity control are not separate phenomena but are closely integrated to properly initiate and sustain stepping. The spinal cord does not simply transmit information to and from the brain. Its physiologic state determines reflex, postural and locomotor control and, therefore, may affect the recovery of the locomotor function in individuals with spinal cord and brain injuries. This review summarizes studies that examine the rhythmogenesis capacity of cervical and lumbosacral neuronal circuitries in humans and its importance in developing central pattern generator-modulating therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Production of human antimicrobial peptide LL-37 in Escherichia coli using a thioredoxin-SUMO dual fusion system.

PubMed

Li, Yifeng

2013-02-01

LL-37 is a human antimicrobial peptide that has been shown to possess multiple functions in host defense. In this report, the peptide was expressed as a fusion with a thioredoxin-SUMO dual-tag. Upon SUMO protease mediated cleavage at the SUMO/peptide junction, LL-37 with its native N-terminus was generated. The released peptide was separated from the dual-tag and cleavage enzyme by size-exclusion chromatography. Mass spectrometry analysis proves that the recombinant peptide has a molecular weight as theoretically expected for its native form. The produced peptide displayed antimicrobial activity against Escherichia coli K-12. On average, 2.4 mg peptide was obtained from one liter of bacterial culture. Thus, the described approach provides an effective alternative for producing active recombinant LL-37 with its natural amino acid sequence in E. coli. Copyright © 2012 Elsevier Inc. All rights reserved.

Groundwater and surface-water interactions and impacts of human activities in the Hailiutu catchment, northwest China

NASA Astrophysics Data System (ADS)

Yang, Zhi; Zhou, Yangxiao; Wenninger, Jochen; Uhlenbrook, Stefan; Wang, Xusheng; Wan, Li

2017-08-01

The interactions between groundwater and surface water have been significantly affected by human activities in the semi-arid Hailiutu catchment, northwest China. Several methods were used to investigate the spatial and temporal interactions between groundwater and surface water. Isotopic and chemical analyses of water samples determined that groundwater discharges to the Hailiutu River, and mass balance equations were employed to estimate groundwater seepage rates along the river using chemical profiles. The hydrograph separation method was used to estimate temporal variations of groundwater discharges to the river. A numerical groundwater model was constructed to simulate groundwater discharges along the river and to analyze effects of water use in the catchment. The simulated seepage rates along the river compare reasonably well with the seepage estimates derived from a chemical profile in 2012. The impacts of human activities (river-water diversion and groundwater abstraction) on the river discharge were analyzed by calculating the differences between the simulated natural groundwater discharge and the measured river discharge. Water use associated with the Hailiutu River increased from 1986 to 1991, reached its highest level from 1992 to 2000, and decreased from 2001 onwards. The reduction of river discharge might have negative impacts on the riparian ecosystem and the water availability for downstream users. The interactions between groundwater and surface water as well as the consequences of human activities should be taken into account when implementing sustainable water resources management in the Hailiutu catchment.

Eye movement-invariant representations in the human visual system.

PubMed

Nishimoto, Shinji; Huth, Alexander G; Bilenko, Natalia Y; Gallant, Jack L

2017-01-01

During natural vision, humans make frequent eye movements but perceive a stable visual world. It is therefore likely that the human visual system contains representations of the visual world that are invariant to eye movements. Here we present an experiment designed to identify visual areas that might contain eye-movement-invariant representations. We used functional MRI to record brain activity from four human subjects who watched natural movies. In one condition subjects were required to fixate steadily, and in the other they were allowed to freely make voluntary eye movements. The movies used in each condition were identical. We reasoned that the brain activity recorded in a visual area that is invariant to eye movement should be similar under fixation and free viewing conditions. In contrast, activity in a visual area that is sensitive to eye movement should differ between fixation and free viewing. We therefore measured the similarity of brain activity across repeated presentations of the same movie within the fixation condition, and separately between the fixation and free viewing conditions. The ratio of these measures was used to determine which brain areas are most likely to contain eye movement-invariant representations. We found that voxels located in early visual areas are strongly affected by eye movements, while voxels in ventral temporal areas are only weakly affected by eye movements. These results suggest that the ventral temporal visual areas contain a stable representation of the visual world that is invariant to eye movements made during natural vision.

Antiproliferative activity of cardenolide glycosides from Asclepias subulata.

PubMed

Rascón-Valenzuela, L; Velázquez, C; Garibay-Escobar, A; Medina-Juárez, L A; Vilegas, W; Robles-Zepeda, R E

2015-08-02

Asclepias subulata Decne. is a shrub occurring in Sonora-Arizona desert (Mexico-USA). The ethnic groups, Seris and Pimas, use this plant for the treatment of sore eyes, gastrointestinal disorders and cancer. To isolate the compounds responsible for antiproliferative activity of the methanol extract of A. subulata. A bioguided fractionation of methanol extract of A. subulata was performed using MTT assay to measure the antiproliferative activity of different compounds on three human cancer cell lines (A549, LS 180 and PC-3), one murine cancer cell line (RAW 264.7) and one human normal cell line (ARPE-19). The methanol extract was partitioned with hexane, ethyl acetate and ethanol. The active fractions, ethanol and residual, were fractioned by silica-column chromatography and active sub-fractions were separated using HPLC. The chemical structures of isolated compounds were elucidated with different chemical and spectroscopic methods. A new cardenolide glycoside, 12, 16-dihydroxycalotropin, and three known, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, were isolated of active sub-fractions. All isolated compounds showed a strong antiproliferative activity in human cancer cells. Calotropin was the more active with IC50 values of 0.0013, 0.06 and 0.41 µM on A549, LS 180 and PC-3 cell lines, respectively; while 12, 16-dihydroxycalotropin reached values of 2.48, 5.62 and 11.70 µM, on the same cells; corotoxigenin 3-O-glucopyranoside had IC50 of 2.64, 3.15 and 6.62 µM and desglucouzarin showed values of 0.90, 6.57 and 6.62, µM. Doxorubicin, positive control, showed IC50 values of 1.78, 6.99 and 3.18 µM, respectively. The isolated compounds had a weak effect on murine cancer cells and human normal cells, exhibiting selectivity to human cancer cells. In this study, we found that 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin are responsible of antiproliferative properties of A. subulata, and that these compounds are highly selective to human cancer cells. Further studies are needed in order to establish the action mechanisms of the isolated compounds. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A combined gene and cell therapy approach for restoration of conduction.

PubMed

Hofshi, Anat; Itzhaki, Ilanit; Gepstein, Amira; Arbel, Gil; Gross, Gil J; Gepstein, Lior

2011-01-01

Abnormal conduction underlies both bradyarrhythmias and re-entrant tachyarrhythmias. However, no practical way exists for restoring or improving conduction in areas of conduction slowing or block. This study sought to test the feasibility of a novel strategy for conduction repair using genetically engineered cells designed to form biological "conducting cables." An in vitro model of conduction block was established using spatially separated, spontaneously contracting, nonsynchronized human embryonic stem cell-derived cardiomyocytes clusters. Immunostaining, dye transfer, intracellular recordings, and multielectrode array (MEA) studies were performed to evaluate the ability of genetically engineered HEK293 cells, expressing the SCN5A-encoded Na(+) channel, to couple with cultured cardiomyocytes and to synchronize their electrical activity. Connexin-43 immunostaining and calcein dye-transfer experiments confirmed the formation of functional gap junctions between the engineered cells and neighboring cardiomyocytes. MEA and intracellular recordings were performed to assess the ability of the engineered cells to restore conduction in the co-cultures. Synchronization was defined by establishment of fixed local activation time differences between the cardiomyocytes clusters and convergence of their activation cycle lengths. Nontransfected control cells were able to induce synchronization between cardiomyocytes clusters separated by distances up to 300 μm (n = 21). In contrast, the Na(+) channel-expressing cells synchronized contractions between clusters separated by up to 1,050 μm, the longest distance studied (n = 23). Finally, engineered cells expressing the voltage-sensitive K(v)1.3 potassium channel prevented synchronization at any distance. Genetically engineered cells, transfected to express Na(+) channels, can form biological conducting cables bridging and coupling spatially separated cardiomyocytes. This novel cell therapy approach might be useful for the development of therapeutic strategies for both bradyarrhythmias and tachyarrhythmias. Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Pension fund activities at Department laboratories managed by the University of California. [Contains Management and Auditor Comments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-09-18

The Department of Energy's (Department) Office of Contractor Human Resource Management, and San Francisco and Albuquerque Field Offices have responsibility for contract administration of the Department's interest in two separate pension plans covering University of California (University) employees at Lawrence Livermore National Laboratory, Lawrence Berkeley Laboratory, and Los Alamos National Laboratory. The purpose of the audit was to review the Department's contract administration of its interest in those pension plans.

Pension fund activities at Department laboratories managed by the University of California

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-09-18

The Department of Energy`s (Department) Office of Contractor Human Resource Management, and San Francisco and Albuquerque Field Offices have responsibility for contract administration of the Department`s interest in two separate pension plans covering University of California (University) employees at Lawrence Livermore National Laboratory, Lawrence Berkeley Laboratory, and Los Alamos National Laboratory. The purpose of the audit was to review the Department`s contract administration of its interest in those pension plans.

Water: A Critical Material Enabling Space Exploration

NASA Technical Reports Server (NTRS)

Pickering, Karen D.

2014-01-01

Water is one of the most critical materials in human spaceflight. The availability of water defines the duration of a space mission; the volume of water required for a long-duration space mission becomes too large, heavy, and expensive for launch vehicles to carry. Since the mission duration is limited by the amount of water a space vehicle can carry, the capability to recycle water enables space exploration. In addition, water management in microgravity impacts spaceflight in other respects, such as the recent emergency termination of a spacewalk caused by free water in an astronaut's spacesuit helmet. A variety of separation technologies are used onboard spacecraft to ensure that water is always available for use, and meets the stringent water quality required for human space exploration. These separation technologies are often adapted for use in a microgravity environment, where water behaves in unique ways. The use of distillation, membrane processes, ion exchange and granular activated carbon will be reviewed. Examples of microgravity effects on operations will also be presented. A roadmap for future technologies, needed to supply water resources for the exploration of Mars, will also be reviewed.

Regional specialization within the human striatum for diverse psychological functions.

PubMed

Pauli, Wolfgang M; O'Reilly, Randall C; Yarkoni, Tal; Wager, Tor D

2016-02-16

Decades of animal and human neuroimaging research have identified distinct, but overlapping, striatal zones, which are interconnected with separable corticostriatal circuits, and are crucial for the organization of functional systems. Despite continuous efforts to subdivide the human striatum based on anatomical and resting-state functional connectivity, characterizing the different psychological processes related to each zone remains a work in progress. Using an unbiased, data-driven approach, we analyzed large-scale coactivation data from 5,809 human imaging studies. We (i) identified five distinct striatal zones that exhibited discrete patterns of coactivation with cortical brain regions across distinct psychological processes and (ii) identified the different psychological processes associated with each zone. We found that the reported pattern of cortical activation reliably predicted which striatal zone was most strongly activated. Critically, activation in each functional zone could be associated with distinct psychological processes directly, rather than inferred indirectly from psychological functions attributed to associated cortices. Consistent with well-established findings, we found an association of the ventral striatum (VS) with reward processing. Confirming less well-established findings, the VS and adjacent anterior caudate were associated with evaluating the value of rewards and actions, respectively. Furthermore, our results confirmed a sometimes overlooked specialization of the posterior caudate nucleus for executive functions, often considered the exclusive domain of frontoparietal cortical circuits. Our findings provide a precise functional map of regional specialization within the human striatum, both in terms of the differential cortical regions and psychological functions associated with each striatal zone.

Regional specialization within the human striatum for diverse psychological functions

PubMed Central

Pauli, Wolfgang M.; O’Reilly, Randall C.; Wager, Tor D.

2016-01-01

Decades of animal and human neuroimaging research have identified distinct, but overlapping, striatal zones, which are interconnected with separable corticostriatal circuits, and are crucial for the organization of functional systems. Despite continuous efforts to subdivide the human striatum based on anatomical and resting-state functional connectivity, characterizing the different psychological processes related to each zone remains a work in progress. Using an unbiased, data-driven approach, we analyzed large-scale coactivation data from 5,809 human imaging studies. We (i) identified five distinct striatal zones that exhibited discrete patterns of coactivation with cortical brain regions across distinct psychological processes and (ii) identified the different psychological processes associated with each zone. We found that the reported pattern of cortical activation reliably predicted which striatal zone was most strongly activated. Critically, activation in each functional zone could be associated with distinct psychological processes directly, rather than inferred indirectly from psychological functions attributed to associated cortices. Consistent with well-established findings, we found an association of the ventral striatum (VS) with reward processing. Confirming less well-established findings, the VS and adjacent anterior caudate were associated with evaluating the value of rewards and actions, respectively. Furthermore, our results confirmed a sometimes overlooked specialization of the posterior caudate nucleus for executive functions, often considered the exclusive domain of frontoparietal cortical circuits. Our findings provide a precise functional map of regional specialization within the human striatum, both in terms of the differential cortical regions and psychological functions associated with each striatal zone. PMID:26831091

The effect of stem cell from human exfoliated deciduous teeth on T lymphocyte proliferation.

PubMed

Alipour, Razieh; Adib, Minoo; Hashemi-Beni, Batool; Sadeghi, Farzaneh

2014-01-01

Mesenchymal stem cells (MSC), a specific type of adult tissue stem cell; have the immunosuppressive effects that make them valuable targets for regenerative medicine and treatment of many human illnesses. Hence, MSC have been the subject of numerous studies. The classical source of MSC is adult bone marrow (BM). Due to many shortcomings of harvesting MSC from BM, finding the alternative sources for MSC is an urgent. Stem cells from human exfoliated deciduous teeth (SHED) are relative new MSC populations that fulfill these criteria but their potential immunosuppressive effect has not been studied enough yet. Thus, in this work the effect of SHED on the proliferation of in vitro activated T lymphocytes were explored. In this study, both mitogen and alloantigen activated T cells were cultured in the presence of different numbers of SHED. In some co-cultures, activated T cells were in direct contact to MSCs and in other co-cultures; they were separated from SHED by a permeable membrane. In all co-cultures, the proliferation of T cells was measured by ELISA Bromodeoxyuridine proliferation assay. In general, our results showed that SHED significantly suppress the proliferation of activated T cells in a dose-dependent manner. Moreover, the suppression was slightly stronger when MSCs were in physical contact to activated T cells. This study showed that SHED likewise other MSC populations can suppress the activation of T lymphocytes, which can be used instead of BM derived MSCs in many investigational and clinical applications.

Correspondence of the brain's functional architecture during activation and rest.

PubMed

Smith, Stephen M; Fox, Peter T; Miller, Karla L; Glahn, David C; Fox, P Mickle; Mackay, Clare E; Filippini, Nicola; Watkins, Kate E; Toro, Roberto; Laird, Angela R; Beckmann, Christian F

2009-08-04

Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is "at rest." In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically "active" even when at "rest."

Teaching for Epistemological Difference: Decentring Norms in Environmental Studies

ERIC Educational Resources Information Center

Barrett, M. J.

2012-01-01

Many environmental educators and philosophers have identified anthropocentrism and the socially constructed separation between humans and "the more-than-human world" (Abram, 1996) as primary root causes of current ecological devastation. This separation is embedded in Western schooling content and structures and is often unintentionally…

The origin of bursts and heavy tails in human dynamics.

PubMed

Barabási, Albert-László

2005-05-12

The dynamics of many social, technological and economic phenomena are driven by individual human actions, turning the quantitative understanding of human behaviour into a central question of modern science. Current models of human dynamics, used from risk assessment to communications, assume that human actions are randomly distributed in time and thus well approximated by Poisson processes. In contrast, there is increasing evidence that the timing of many human activities, ranging from communication to entertainment and work patterns, follow non-Poisson statistics, characterized by bursts of rapidly occurring events separated by long periods of inactivity. Here I show that the bursty nature of human behaviour is a consequence of a decision-based queuing process: when individuals execute tasks based on some perceived priority, the timing of the tasks will be heavy tailed, with most tasks being rapidly executed, whereas a few experience very long waiting times. In contrast, random or priority blind execution is well approximated by uniform inter-event statistics. These finding have important implications, ranging from resource management to service allocation, in both communications and retail.

Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin

PubMed Central

Wang, Ying; Lomakin, Aleksey; Latypov, Ramil F.; Benedek, George B.

2011-01-01

We report the observation of liquid-liquid phase separation in a solution of human monoclonal antibody, IgG2, and the effects of human serum albumin, a major blood protein, on this phase separation. We find a significant reduction of phase separation temperature in the presence of albumin, and a preferential partitioning of the albumin into the antibody-rich phase. We provide a general thermodynamic analysis of the antibody-albumin mixture phase diagram and relate its features to the magnitude of the effective interprotein interactions. Our analysis suggests that additives (HSA in this report), which have moderate attraction with antibody molecules, may be used to forestall undesirable proetin condensation in antibody solutions. Our findings are relevant to understanding the stability of pharmaceutical solutions of antibodies and the mechanisms of cryoglobulinemia. PMID:21921237

Common ecology quantifies human insurgency.

PubMed

Bohorquez, Juan Camilo; Gourley, Sean; Dixon, Alexander R; Spagat, Michael; Johnson, Neil F

2009-12-17

Many collective human activities, including violence, have been shown to exhibit universal patterns. The size distributions of casualties both in whole wars from 1816 to 1980 and terrorist attacks have separately been shown to follow approximate power-law distributions. However, the possibility of universal patterns ranging across wars in the size distribution or timing of within-conflict events has barely been explored. Here we show that the sizes and timing of violent events within different insurgent conflicts exhibit remarkable similarities. We propose a unified model of human insurgency that reproduces these commonalities, and explains conflict-specific variations quantitatively in terms of underlying rules of engagement. Our model treats each insurgent population as an ecology of dynamically evolving, self-organized groups following common decision-making processes. Our model is consistent with several recent hypotheses about modern insurgency, is robust to many generalizations, and establishes a quantitative connection between human insurgency, global terrorism and ecology. Its similarity to financial market models provides a surprising link between violent and non-violent forms of human behaviour.

Modeling bursts and heavy tails in human dynamics

NASA Astrophysics Data System (ADS)

Vázquez, Alexei; Oliveira, João Gama; Dezsö, Zoltán; Goh, Kwang-Il; Kondor, Imre; Barabási, Albert-László

2006-03-01

The dynamics of many social, technological and economic phenomena are driven by individual human actions, turning the quantitative understanding of human behavior into a central question of modern science. Current models of human dynamics, used from risk assessment to communications, assume that human actions are randomly distributed in time and thus well approximated by Poisson processes. Here we provide direct evidence that for five human activity patterns, such as email and letter based communications, web browsing, library visits and stock trading, the timing of individual human actions follow non-Poisson statistics, characterized by bursts of rapidly occurring events separated by long periods of inactivity. We show that the bursty nature of human behavior is a consequence of a decision based queuing process: when individuals execute tasks based on some perceived priority, the timing of the tasks will be heavy tailed, most tasks being rapidly executed, while a few experiencing very long waiting times. In contrast, priority blind execution is well approximated by uniform interevent statistics. We discuss two queuing models that capture human activity. The first model assumes that there are no limitations on the number of tasks an individual can hadle at any time, predicting that the waiting time of the individual tasks follow a heavy tailed distribution P(τw)˜τw-α with α=3/2 . The second model imposes limitations on the queue length, resulting in a heavy tailed waiting time distribution characterized by α=1 . We provide empirical evidence supporting the relevance of these two models to human activity patterns, showing that while emails, web browsing and library visitation display α=1 , the surface mail based communication belongs to the α=3/2 universality class. Finally, we discuss possible extension of the proposed queuing models and outline some future challenges in exploring the statistical mechanics of human dynamics.

Modeling bursts and heavy tails in human dynamics.

PubMed

Vázquez, Alexei; Oliveira, João Gama; Dezsö, Zoltán; Goh, Kwang-Il; Kondor, Imre; Barabási, Albert-László

2006-03-01

The dynamics of many social, technological and economic phenomena are driven by individual human actions, turning the quantitative understanding of human behavior into a central question of modern science. Current models of human dynamics, used from risk assessment to communications, assume that human actions are randomly distributed in time and thus well approximated by Poisson processes. Here we provide direct evidence that for five human activity patterns, such as email and letter based communications, web browsing, library visits and stock trading, the timing of individual human actions follow non-Poisson statistics, characterized by bursts of rapidly occurring events separated by long periods of inactivity. We show that the bursty nature of human behavior is a consequence of a decision based queuing process: when individuals execute tasks based on some perceived priority, the timing of the tasks will be heavy tailed, most tasks being rapidly executed, while a few experiencing very long waiting times. In contrast, priority blind execution is well approximated by uniform interevent statistics. We discuss two queuing models that capture human activity. The first model assumes that there are no limitations on the number of tasks an individual can handle at any time, predicting that the waiting time of the individual tasks follow a heavy tailed distribution P(tau(w)) approximately tau(w)(-alpha) with alpha=3/2. The second model imposes limitations on the queue length, resulting in a heavy tailed waiting time distribution characterized by alpha=1. We provide empirical evidence supporting the relevance of these two models to human activity patterns, showing that while emails, web browsing and library visitation display alpha=1, the surface mail based communication belongs to the alpha=3/2 universality class. Finally, we discuss possible extension of the proposed queuing models and outline some future challenges in exploring the statistical mechanics of human dynamics.

Effects of Selected Task Performance Criteria at Initiating Adaptive Task Real locations

NASA Technical Reports Server (NTRS)

Montgomery, Demaris A.

2001-01-01

In the current report various performance assessment methods used to initiate mode transfers between manual control and automation for adaptive task reallocation were tested. Participants monitored two secondary tasks for critical events while actively controlling a process in a fictional system. One of the secondary monitoring tasks could be automated whenever operators' performance was below acceptable levels. Automation of the secondary task and transfer of the secondary task back to manual control were either human- or machine-initiated. Human-initiated transfers were based on the operator's assessment of the current task demands while machine-initiated transfers were based on the operators' performance. Different performance assessment methods were tested in two separate experiments.

Herbs and spices: characterization and quantitation of biologically-active markers for routine quality control by multiple headspace solid-phase microextraction combined with separative or non-separative analysis.

PubMed

Sgorbini, Barbara; Bicchi, Carlo; Cagliero, Cecilia; Cordero, Chiara; Liberto, Erica; Rubiolo, Patrizia

2015-01-09

Herbs and spices are used worldwide as food flavoring, thus determination of their identity, origin, and quality is mandatory for safe human consumption. An analysis strategy based on separative (HS-SPME-GC-MS) and non-separative (HS-SPME-MS) approaches is proposed for the volatile fraction of herbs and spices, for quality control and to quantify the aromatic markers with a single analysis directly on the plant material as such. Eight-to-ten lots of each of the following herbs/spices were considered: cloves (Syzygium aromaticum (L.) Merr. & Perry), American peppertree (Schinus molle L.), black pepper and white pepper (Piper nigrum L.), rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.). Homogeneity, origin, and chemotypes of the investigated lots of each herb/spice were defined by fingerprinting, through statistical elaboration with principal component analysis (PCA). Characterizing aromatic markers were directly quantified on the solid matrix through multiple headspace extraction-HS-SPME (MHS-SPME). Reliable results were obtained with both separative and non-separative methods (where the latter were applicable); the two were in full agreement, RSD% ranging from 1.8 to 7.7% for eugenol in cloves, 2.2-18.4% for carvacrol+thymol in thyme, and 3.1-16.8% for thujones in sage. Copyright © 2014 Elsevier B.V. All rights reserved.

Measurement of caffeine and its three primary metabolites in human plasma by HPLC-ESI-MS/MS and clinical application.

PubMed

Chen, Feng; Hu, Zhe-Yi; Parker, Robert B; Laizure, S Casey

2017-06-01

Caffeine is a mild stimulant with significant potential for abuse, being consumed in larger doses with the widespread availability of energy drinks and by novel routes of administration such as inspired powder, oral sprays and electronic cigarettes. How these recent changes in caffeine consumption affecting caffeine disposition and abuse potential is of growing concern. In the study of caffeine disposition in humans, it is common to only measure the caffeine concentration; however, caffeine's three major metabolites (paraxanthine, theobromine and theophylline) retain central nervous system stimulant activity that may contribute to the overall pharmacological activity and toxicity. Therefore, it would be scientifically more rigorous to measure caffeine and its major metabolites in the evaluation of caffeine disposition in human subjects. Herein, we report a method for the simultaneous quantification of caffeine and its three major metabolites in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). Human plasma samples were treated by simple protein precipitation and the analytes were separated using a 6 min gradient program. Precision and accuracy were well within in the 15% acceptance range. The simple sample preparation, short runtime, sensitivity and the inclusion of caffeine's major metabolites make this assay methodology optimal for the study of caffeine's pharmacokinetics and pharmacodynamics in human subjects. Copyright © 2016 John Wiley & Sons, Ltd.

An alternative perspective on assistive technology: the Person-Environment-Tool (PET) model.

PubMed

Jarl, Gustav; Lundqvist, Lars-Olov

2018-04-20

The medical and social models of disability are based on a dichotomy that categorizes people as able-bodied or disabled. In contrast, the biopsychosocial model, which forms the basis for the International Classification of Functioning, Disability and Health (ICF), suggests a universalistic perspective on human functioning, encompassing all human beings. In this article we argue that the artificial separation of function-enhancing technology into assistive technology (AT) and mainstream technology might be one of the barriers to a universalistic view of human functioning. Thus, an alternative view of AT is needed. The aim of this article was to construct a conceptual model to demonstrate how all human activities and participation depend on factors related to the person, environment, and tools, emphasizing a universalistic perspective on human functioning. In the Person-Environment-Tool (PET) model, a person's activity and participation are described as a function of factors related to the person, environment, and tool, drawing on various ICF components. Importantly, the PET model makes no distinction between people of different ability levels, between environmental modifications intended for people of different ability levels, or between different function-enhancing technologies (AT and mainstream technology). A fictive patient case is used to illustrate how the universalistic view of the PET model lead to a different approach in rehabilitation. The PET model supports a universalistic view of technology use, environmental adaptations, and variations in human functioning.

5 CFR 5501.102 - Designation of HHS components as separate agencies.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Designation of HHS components as separate agencies. 5501.102 Section 5501.102 Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5501...

5 CFR 5501.102 - Designation of HHS components as separate agencies.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Designation of HHS components as separate agencies. 5501.102 Section 5501.102 Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5501...

5 CFR 5501.102 - Designation of HHS components as separate agencies.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Designation of HHS components as separate agencies. 5501.102 Section 5501.102 Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5501...

5 CFR 5501.102 - Designation of HHS components as separate agencies.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Designation of HHS components as separate agencies. 5501.102 Section 5501.102 Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5501...

5 CFR 5501.102 - Designation of HHS components as separate agencies.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Designation of HHS components as separate agencies. 5501.102 Section 5501.102 Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5501...

Bee venom processes human skin lipids for presentation by CD1a

PubMed Central

Bourgeois, Elvire A.; Subramaniam, Sumithra; Cheng, Tan-Yun; De Jong, Annemieke; Layre, Emilie; Ly, Dalam; Salimi, Maryam; Legaspi, Annaliza; Modlin, Robert L.; Salio, Mariolina; Cerundolo, Vincenzo

2015-01-01

Venoms frequently co-opt host immune responses, so study of their mode of action can provide insight into novel inflammatory pathways. Using bee and wasp venom responses as a model system, we investigated whether venoms contain CD1-presented antigens. Here, we show that venoms activate human T cells via CD1a proteins. Whereas CD1 proteins typically present lipids, chromatographic separation of venoms unexpectedly showed that stimulatory factors partition into protein-containing fractions. This finding was explained by demonstrating that bee venom–derived phospholipase A2 (PLA2) activates T cells through generation of small neoantigens, such as free fatty acids and lysophospholipids, from common phosphodiacylglycerides. Patient studies showed that injected PLA2 generates lysophospholipids within human skin in vivo, and polyclonal T cell responses are dependent on CD1a protein and PLA2. These findings support a previously unknown skin immune response based on T cell recognition of CD1a proteins and lipid neoantigen generated in vivo by phospholipases. The findings have implications for skin barrier sensing by T cells and mechanisms underlying phospholipase-dependent inflammatory skin disease. PMID:25584012

Analysis of Traffic Conflicts in a Mixed-Airspace Evaluation of Airborne Separation Assurance

NASA Technical Reports Server (NTRS)

Lewis, Timothy A.

2013-01-01

A pair of human-in-the-loop simulation evaluations of a distributed air/ground separation assurance system have been conducted to investigate the function allocation between humans and automation systems as well as ground-based and airborne agents in the Next Generation Air Transportation System and beyond. This paper focuses on an analysis of certain critical conflicts observed between self-separating aircraft and ground-managed traffic in the same airspace. The principal cause of each conflict is identified and potential mitigations are discussed, such as: the sharing of trajectory intent information between the ground and the air; more cautious trajectory planning by the self-separating aircraft; and more equitable rules-of-the-road between the self-separating aircraft and ground-managed aircraft. This analysis will inform the ongoing design of an airborne separation assurance automation tool.

Phase Separation and Crystallization of Hemoglobin C in Transgenic Mouse and Human Erythrocytes

PubMed Central

Canterino, Joseph E.; Galkin, Oleg; Vekilov, Peter G.; Hirsch, Rhoda Elison

2008-01-01

Individuals expressing hemoglobin C (β6 Glu→Lys) present red blood cells (RBC) with intraerythrocytic crystals that form when hemoglobin (Hb) is oxygenated. Our earlier in vitro liquid-liquid (L-L) phase separation studies demonstrated that liganded HbC exhibits a stronger net intermolecular attraction with a longer range than liganded HbS or HbA, and that L-L phase separation preceded and enhanced crystallization. We now present evidence for the role of phase separation in HbC crystallization in the RBC, and the role of the RBC membrane as a nucleation center. RBC obtained from both human homozygous HbC patients and transgenic mice expressing only human HbC were studied by bright-field and differential interference contrast video-enhanced microscopy. RBC were exposed to hypertonic NaCl solution (1.5–3%) to induce crystallization within an appropriate experimental time frame. L-L phase separation occurred inside the RBC, which in turn enhanced the formation of intraerythrocytic crystals. RBC L-L phase separation and crystallization comply with the thermodynamic and kinetics laws established through in vitro studies of phase transformations. This is the first report, to the best of our knowledge, to capture a temporal view of intraerythrocytic HbC phase separation, crystal formation, and dissolution. PMID:18621841

Attentional Bias in Human Category Learning: The Case of Deep Learning.

PubMed

Hanson, Catherine; Caglar, Leyla Roskan; Hanson, Stephen José

2018-01-01

Category learning performance is influenced by both the nature of the category's structure and the way category features are processed during learning. Shepard (1964, 1987) showed that stimuli can have structures with features that are statistically uncorrelated (separable) or statistically correlated (integral) within categories. Humans find it much easier to learn categories having separable features, especially when attention to only a subset of relevant features is required, and harder to learn categories having integral features, which require consideration of all of the available features and integration of all the relevant category features satisfying the category rule (Garner, 1974). In contrast to humans, a single hidden layer backpropagation (BP) neural network has been shown to learn both separable and integral categories equally easily, independent of the category rule (Kruschke, 1993). This "failure" to replicate human category performance appeared to be strong evidence that connectionist networks were incapable of modeling human attentional bias. We tested the presumed limitations of attentional bias in networks in two ways: (1) by having networks learn categories with exemplars that have high feature complexity in contrast to the low dimensional stimuli previously used, and (2) by investigating whether a Deep Learning (DL) network, which has demonstrated humanlike performance in many different kinds of tasks (language translation, autonomous driving, etc.), would display human-like attentional bias during category learning. We were able to show a number of interesting results. First, we replicated the failure of BP to differentially process integral and separable category structures when low dimensional stimuli are used (Garner, 1974; Kruschke, 1993). Second, we show that using the same low dimensional stimuli, Deep Learning (DL), unlike BP but similar to humans, learns separable category structures more quickly than integral category structures. Third, we show that even BP can exhibit human like learning differences between integral and separable category structures when high dimensional stimuli (face exemplars) are used. We conclude, after visualizing the hidden unit representations, that DL appears to extend initial learning due to feature development thereby reducing destructive feature competition by incrementally refining feature detectors throughout later layers until a tipping point (in terms of error) is reached resulting in rapid asymptotic learning.

Muscle contraction induced arterial shear stress increases endothelial nitric oxide synthase phosphorylation in humans.

PubMed

Casey, Darren P; Ueda, Kenichi; Wegman-Points, Lauren; Pierce, Gary L

2017-10-01

We determined if local increases in brachial artery shear during repetitive muscle contractions induce changes in protein expression of endothelial nitric oxide synthase (eNOS) and/or phosphorylated (p-)eNOS at Ser 1177 , the primary activation site on eNOS, in endothelial cells (ECs) of humans. Seven young male subjects (25 ± 1 yr) performed 20 separate bouts (3 min each) of rhythmic forearm exercise at 20% of maximum over a 2-h period. Each bout of exercise was separated by 3 min of rest. An additional six male subjects (24 ± 1 yr) served as time controls (no exercise). ECs were freshly isolated from the brachial artery using sterile J-wires through an arterial catheter at baseline and again after the 2-h exercise or time control period. Expression of eNOS or p-eNOS Ser 1177 in ECs was determined via immunofluorescence. Brachial artery mean shear rate was elevated compared with baseline and the time control group throughout the 2-h exercise protocol ( P < 0.001). p-eNOS Ser 1177 expression was increased 57% in ECs in the exercise group [0.06 ± 0.01 vs. 0.10 ± 0.02 arbitrary units (au), P = 0.02] but not in the time control group (0.08 ± 0.01 vs. 0.07 ± 0.01 au, P = 0.72). In contrast, total eNOS expression did not change in either the exercise (0.13 ± 0.04 vs. 0.12 ± 0.03 au) or time control (0.12 ± 0.03 vs. 0.11 ± 0.03 au) group ( P > 0.05 for both). Our novel results suggest that elevations in brachial artery shear increase eNOS Ser 1177 phosphorylation in the absence of changes in total eNOS in ECs of young healthy male subjects, suggesting that this model is sufficient to alter posttranslational modification of eNOS activity in vivo in humans. NEW & NOTEWORTHY Elevations in brachial artery shear in response to forearm exercise increased endothelial nitric oxide synthase Ser 1177 phosphorylation in brachial artery endothelial cells of healthy humans. Our present study provides the first evidence in humans that muscle contraction-induced increases in conduit arterial shear lead to in vivo posttranslational modification of endothelial nitric oxide synthase activity in endothelial cells. Copyright © 2017 the American Physiological Society.

Gasdermins: Effectors of Pyroptosis.

PubMed

Kovacs, Stephen B; Miao, Edward A

2017-09-01

Pyroptosis is a form of lytic programmed cell death initiated by inflammasomes, which detect cytosolic contamination or perturbation. This drives activation of caspase-1 or caspase-11/4/5, which cleave gasdermin D, separating its N-terminal pore-forming domain (PFD) from the C-terminal repressor domain (RD). The PFD oligomerizes to form large pores in the membrane that drive swelling and membrane rupture. Gasdermin D is one of six (in humans) gasdermin family members; several other gasdermins have also been shown to form pores that cause pyroptosis after cleavage to activate their PFDs. One of these, gasdermin E, is activated by caspase-3 cleavage. We review our current understanding of pyroptosis as well as current knowledge of the gasdermin family. Copyright © 2017 Elsevier Ltd. All rights reserved.

An Overview of the NASA Aviation Safety Program (AVSP) Systemwide Accident Prevention (SWAP) Human Performance Modeling (HPM) Element

NASA Technical Reports Server (NTRS)

Foyle, David C.; Goodman, Allen; Hooley, Becky L.

2003-01-01

An overview is provided of the Human Performance Modeling (HPM) element within the NASA Aviation Safety Program (AvSP). Two separate model development tracks for performance modeling of real-world aviation environments are described: the first focuses on the advancement of cognitive modeling tools for system design, while the second centers on a prescriptive engineering model of activity tracking for error detection and analysis. A progressive implementation strategy for both tracks is discussed in which increasingly more complex, safety-relevant applications are undertaken to extend the state-of-the-art, as well as to reveal potential human-system vulnerabilities in the aviation domain. Of particular interest is the ability to predict the precursors to error and to assess potential mitigation strategies associated with the operational use of future flight deck technologies.

The functional architecture of the human body: assessing body representation by sorting body parts and activities.

PubMed

Bläsing, Bettina; Schack, Thomas; Brugger, Peter

2010-05-01

We investigated mental representations of body parts and body-related activities in two subjects with congenitally absent limbs (one with, the other without phantom sensations), a wheelchair sports group of paraplegic participants, and two groups of participants with intact limbs. To analyse mental representation structures, we applied Structure Dimensional Analysis. Verbal labels indicating body parts and related activities were presented in randomized lists that had to be sorted according to a hierarchical splitting paradigm. Participants were required to group the items according to whether or not they were considered related, based on their own body perception. Results of the groups of physically intact and paraplegic participants revealed separate clusters for the lower body, upper body, fingers and head. The participant with congenital phantom limbs also showed a clear separation between upper and lower body (but not between fingers and hands). In the participant without phantom sensations of the absent arms, no such modularity emerged, but the specific practice of his right foot in communication and daily routines was reflected. Sorting verbal labels of body parts and activities appears a useful method to assess body representation in individuals with special body anatomy or function and leads to conclusions largely compatible with other assessment procedures.

Recovering fNIRS brain signals: physiological interference suppression with independent component analysis

NASA Astrophysics Data System (ADS)

Zhang, Y.; Shi, M.; Sun, J.; Yang, C.; Zhang, Yajuan; Scopesi, F.; Makobore, P.; Chin, C.; Serra, G.; Wickramasinghe, Y. A. B. D.; Rolfe, P.

2015-02-01

Brain activity can be monitored non-invasively by functional near-infrared spectroscopy (fNIRS), which has several advantages in comparison with other methods, such as flexibility, portability, low cost and fewer physical restrictions. However, in practice fNIRS measurements are often contaminated by physiological interference arising from cardiac contraction, breathing and blood pressure fluctuations, thereby severely limiting the utility of the method. Hence, further improvement is necessary to reduce or eliminate such interference in order that the evoked brain activity information can be extracted reliably from fNIRS data. In the present paper, the multi-distance fNIRS probe configuration has been adopted. The short-distance fNIRS measurement is treated as the virtual channel and the long-distance fNIRS measurement is treated as the measurement channel. Independent component analysis (ICA) is employed for the fNIRS recordings to separate the brain signals and the interference. Least-absolute deviation (LAD) estimator is employed to recover the brain activity signals. We also utilized Monte Carlo simulations based on a five-layer model of the adult human head to evaluate our methodology. The results demonstrate that the ICA algorithm has the potential to separate physiological interference in fNIRS data and the LAD estimator could be a useful criterion to recover the brain activity signals.

Human reinforcement learning subdivides structured action spaces by learning effector-specific values

PubMed Central

Gershman, Samuel J.; Pesaran, Bijan; Daw, Nathaniel D.

2009-01-01

Humans and animals are endowed with a large number of effectors. Although this enables great behavioral flexibility, it presents an equally formidable reinforcement learning problem of discovering which actions are most valuable, due to the high dimensionality of the action space. An unresolved question is how neural systems for reinforcement learning – such as prediction error signals for action valuation associated with dopamine and the striatum – can cope with this “curse of dimensionality.” We propose a reinforcement learning framework that allows for learned action valuations to be decomposed into effector-specific components when appropriate to a task, and test it by studying to what extent human behavior and BOLD activity can exploit such a decomposition in a multieffector choice task. Subjects made simultaneous decisions with their left and right hands and received separate reward feedback for each hand movement. We found that choice behavior was better described by a learning model that decomposed the values of bimanual movements into separate values for each effector, rather than a traditional model that treated the bimanual actions as unitary with a single value. A decomposition of value into effector-specific components was also observed in value-related BOLD signaling, in the form of lateralized biases in striatal correlates of prediction error and anticipatory value correlates in the intraparietal sulcus. These results suggest that the human brain can use decomposed value representations to “divide and conquer” reinforcement learning over high-dimensional action spaces. PMID:19864565

Human reinforcement learning subdivides structured action spaces by learning effector-specific values.

PubMed

Gershman, Samuel J; Pesaran, Bijan; Daw, Nathaniel D

2009-10-28

Humans and animals are endowed with a large number of effectors. Although this enables great behavioral flexibility, it presents an equally formidable reinforcement learning problem of discovering which actions are most valuable because of the high dimensionality of the action space. An unresolved question is how neural systems for reinforcement learning-such as prediction error signals for action valuation associated with dopamine and the striatum-can cope with this "curse of dimensionality." We propose a reinforcement learning framework that allows for learned action valuations to be decomposed into effector-specific components when appropriate to a task, and test it by studying to what extent human behavior and blood oxygen level-dependent (BOLD) activity can exploit such a decomposition in a multieffector choice task. Subjects made simultaneous decisions with their left and right hands and received separate reward feedback for each hand movement. We found that choice behavior was better described by a learning model that decomposed the values of bimanual movements into separate values for each effector, rather than a traditional model that treated the bimanual actions as unitary with a single value. A decomposition of value into effector-specific components was also observed in value-related BOLD signaling, in the form of lateralized biases in striatal correlates of prediction error and anticipatory value correlates in the intraparietal sulcus. These results suggest that the human brain can use decomposed value representations to "divide and conquer" reinforcement learning over high-dimensional action spaces.

Processing of pitch and location in human auditory cortex during visual and auditory tasks.

PubMed

Häkkinen, Suvi; Ovaska, Noora; Rinne, Teemu

2015-01-01

The relationship between stimulus-dependent and task-dependent activations in human auditory cortex (AC) during pitch and location processing is not well understood. In the present functional magnetic resonance imaging study, we investigated the processing of task-irrelevant and task-relevant pitch and location during discrimination, n-back, and visual tasks. We tested three hypotheses: (1) According to prevailing auditory models, stimulus-dependent processing of pitch and location should be associated with enhanced activations in distinct areas of the anterior and posterior superior temporal gyrus (STG), respectively. (2) Based on our previous studies, task-dependent activation patterns during discrimination and n-back tasks should be similar when these tasks are performed on sounds varying in pitch or location. (3) Previous studies in humans and animals suggest that pitch and location tasks should enhance activations especially in those areas that also show activation enhancements associated with stimulus-dependent pitch and location processing, respectively. Consistent with our hypotheses, we found stimulus-dependent sensitivity to pitch and location in anterolateral STG and anterior planum temporale (PT), respectively, in line with the view that these features are processed in separate parallel pathways. Further, task-dependent activations during discrimination and n-back tasks were associated with enhanced activations in anterior/posterior STG and posterior STG/inferior parietal lobule (IPL) irrespective of stimulus features. However, direct comparisons between pitch and location tasks performed on identical sounds revealed no significant activation differences. These results suggest that activations during pitch and location tasks are not strongly affected by enhanced stimulus-dependent activations to pitch or location. We also found that activations in PT were strongly modulated by task requirements and that areas in the inferior parietal lobule (IPL) showed task-dependent activation modulations, but no systematic activations to pitch or location. Based on these results, we argue that activations during pitch and location tasks cannot be explained by enhanced stimulus-specific processing alone, but rather that activations in human AC depend in a complex manner on the requirements of the task at hand.

Processing of pitch and location in human auditory cortex during visual and auditory tasks

PubMed Central

Häkkinen, Suvi; Ovaska, Noora; Rinne, Teemu

2015-01-01

The relationship between stimulus-dependent and task-dependent activations in human auditory cortex (AC) during pitch and location processing is not well understood. In the present functional magnetic resonance imaging study, we investigated the processing of task-irrelevant and task-relevant pitch and location during discrimination, n-back, and visual tasks. We tested three hypotheses: (1) According to prevailing auditory models, stimulus-dependent processing of pitch and location should be associated with enhanced activations in distinct areas of the anterior and posterior superior temporal gyrus (STG), respectively. (2) Based on our previous studies, task-dependent activation patterns during discrimination and n-back tasks should be similar when these tasks are performed on sounds varying in pitch or location. (3) Previous studies in humans and animals suggest that pitch and location tasks should enhance activations especially in those areas that also show activation enhancements associated with stimulus-dependent pitch and location processing, respectively. Consistent with our hypotheses, we found stimulus-dependent sensitivity to pitch and location in anterolateral STG and anterior planum temporale (PT), respectively, in line with the view that these features are processed in separate parallel pathways. Further, task-dependent activations during discrimination and n-back tasks were associated with enhanced activations in anterior/posterior STG and posterior STG/inferior parietal lobule (IPL) irrespective of stimulus features. However, direct comparisons between pitch and location tasks performed on identical sounds revealed no significant activation differences. These results suggest that activations during pitch and location tasks are not strongly affected by enhanced stimulus-dependent activations to pitch or location. We also found that activations in PT were strongly modulated by task requirements and that areas in the inferior parietal lobule (IPL) showed task-dependent activation modulations, but no systematic activations to pitch or location. Based on these results, we argue that activations during pitch and location tasks cannot be explained by enhanced stimulus-specific processing alone, but rather that activations in human AC depend in a complex manner on the requirements of the task at hand. PMID:26594185

Contributions of immunoaffinity chromatography to deep proteome profiling of human biofluids

DOE PAGES

Wu, Chaochao; Duan, Jicheng; Liu, Tao; ...

2016-01-12

Human biofluids, especially blood plasma or serum, hold great potential as the sources of candidate biomarkers for various diseases; however, the enormous dynamic range of protein concentrations in biofluids represents a significant analytical challenge for detecting promising low-abundance proteins. Over the last decade, various immunoaffinity chromatographic methods have been developed and routinely applied for separating low-abundance proteins from the high- and moderate-abundance proteins, thus enabling much more effective detection of low-abundance proteins. Herein, we review the advances of immunoaffinity separation methods and their contributions to the proteomic applications in human biofluids. The limitations and future perspectives of immunoaffinity separation methodsmore » are also discussed.« less

Multifunctional Nutrient-Binding Proteins Adapt Human Symbiotic Bacteria for Glycan Competition in the Gut by Separately Promoting Enhanced Sensing and Catalysis

PubMed Central

Cameron, Elizabeth A.; Kwiatkowski, Kurt J.; Lee, Byung-Hoo; Hamaker, Bruce R.; Koropatkin, Nicole M.

2014-01-01

ABSTRACT To compete for the dynamic stream of nutrients flowing into their ecosystem, colonic bacteria must respond rapidly to new resources and then catabolize them efficiently once they are detected. The Bacteroides thetaiotaomicron starch utilization system (Sus) is a model for nutrient acquisition by symbiotic gut bacteria, which harbor thousands of related Sus-like systems. Structural investigation of the four Sus outer membrane proteins (SusD, -E, -F, and -G) revealed that they contain a total of eight starch-binding sites that we demonstrated, using genetic and biochemical approaches, to play distinct roles in starch metabolism in vitro and in vivo in gnotobiotic mice. SusD, whose homologs are abundant in the human microbiome, is critical for the initial sensing of available starch, allowing sus transcriptional activation at much lower concentrations than without this function. In contrast, seven additional binding sites across SusE, -F, and -G are dispensable for sus activation. However, they optimize the rate of growth on starch in a manner dependent on the expression of the bacterial polysaccharide capsule, suggesting that they have evolved to offset the diffusion barrier created by this structure. These findings demonstrate how proteins with similar biochemical behavior can serve orthogonal functions during different stages of cellular adaptation to nutrients. Finally, we demonstrated in gnotobiotic mice fed a starch-rich diet that the Sus binding sites confer a competitive advantage to B. thetaiotaomicron in vivo in a manner that is dependent on other colonizing microbes. This study reveals how numerically dominant families of carbohydrate-binding proteins in the human microbiome fulfill separate and sometimes cooperative roles to optimize gut commensal bacteria for nutrient acquisition. PMID:25205092

Convergence of semantics and emotional expression within the IFG pars orbitalis.

PubMed

Belyk, Michel; Brown, Steven; Lim, Jessica; Kotz, Sonja A

2017-08-01

Humans communicate through a combination of linguistic and emotional channels, including propositional speech, writing, sign language, music, but also prosodic, facial, and gestural expression. These channels can be interpreted separately or they can be integrated to multimodally convey complex meanings. Neural models of the perception of semantics and emotion include nodes for both functions in the inferior frontal gyrus pars orbitalis (IFGorb). However, it is not known whether this convergence involves a common functional zone or instead specialized subregions that process semantics and emotion separately. To address this, we performed Kernel Density Estimation meta-analyses of published neuroimaging studies of the perception of semantics or emotion that reported activation in the IFGorb. The results demonstrated that the IFGorb contains two zones with distinct functional profiles. A lateral zone, situated immediately ventral to Broca's area, was implicated in both semantics and emotion. Another zone, deep within the ventral frontal operculum, was engaged almost exclusively by studies of emotion. Follow-up analysis using Meta-Analytic Connectivity Modeling demonstrated that both zones were frequently co-activated with a common network of sensory, motor, and limbic structures, although the lateral zone had a greater association with prefrontal cortical areas involved in executive function. The status of the lateral IFGorb as a point of convergence between the networks for processing semantic and emotional content across modalities of communication is intriguing since this structure is preserved across primates with limited semantic abilities. Hence, the IFGorb may have initially evolved to support the comprehension of emotional signals, being later co-opted to support semantic communication in humans by forming new connections with brain regions that formed the human semantic network. Copyright © 2017 Elsevier Inc. All rights reserved.

A developed determination of midazolam and 1'-hydroxymidazolam in plasma by liquid chromatography-mass spectrometry: application of human pharmacokinetic study for measurement of CYP3A activity.

PubMed

Shimizu, Mikiko; Uno, Tsukasa; Tamura, Hiro-omi; Kanazawa, Hideko; Murakami, Isao; Sugawara, Kazunobu; Tateishi, Tomonori

2007-03-01

This paper describes sensitive and reliable determination of midazolam (MDZ) and its major metabolite 1'-hydroxymidazolam (1-OHMDZ) in human plasma by liquid chromatography-mass spectrometry (LC-MS) with a sonic spray ionization (SSI) interface. MDZ, 1-OHMDZ and diazepam as an internal standard were extracted from 1ml of alkalinized plasma using n-hexane-chloroform (70:30, v/v). The extract was injected into an analytical column (YMC-Pak Pro C(18), 50mmx2.0mmi.d.). The mobile phase for separation consisted of 10mM ammonium acetate and methanol (50:50, v/v) and was delivered at a flow-rate of 0.2ml/min. The drift voltage was 100V. The sampling aperture was heated at 120 degrees C and the shield temperature was 260 degrees C. The total time for chromatographic separation was less than 16min. The validated concentration ranges of this method were 0.25-50ng/ml for both MDZ and 1-OHMDZ. Mean recoveries were 93.6% for MDZ and 86.6% for 1-OHMDZ. Intra- and inter-day coefficient variations were less than 6.5 and 5.5% for MDZ, and 6.1 and 5.7% for 1-OHMDZ at 0.3, 4, 20 and 40ng/ml. The limits of quantification were 0.25ng/ml for both MDZ and 1-OHMDZ. This method was sensitive and reliable enough for pharmacokinetic studies on healthy volunteers, and was applied for the measurement of CYP3A activity in humans after an intravenous (1mg) and a single-oral administration (2mg) of subtherapeutic MDZ dose.

Inferring human population size and separation history from multiple genome sequences.

PubMed

Schiffels, Stephan; Durbin, Richard

2014-08-01

The availability of complete human genome sequences from populations across the world has given rise to new population genetic inference methods that explicitly model ancestral relationships under recombination and mutation. So far, application of these methods to evolutionary history more recent than 20,000-30,000 years ago and to population separations has been limited. Here we present a new method that overcomes these shortcomings. The multiple sequentially Markovian coalescent (MSMC) analyzes the observed pattern of mutations in multiple individuals, focusing on the first coalescence between any two individuals. Results from applying MSMC to genome sequences from nine populations across the world suggest that the genetic separation of non-African ancestors from African Yoruban ancestors started long before 50,000 years ago and give information about human population history as recent as 2,000 years ago, including the bottleneck in the peopling of the Americas and separations within Africa, East Asia and Europe.

A reverse-translational study of dysfunctional exploration in psychiatric disorders: from mice to men.

PubMed

Perry, William; Minassian, Arpi; Paulus, Martin P; Young, Jared W; Kincaid, Meegin J; Ferguson, Eliza J; Henry, Brook L; Zhuang, Xiaoxi; Masten, Virginia L; Sharp, Richard F; Geyer, Mark A

2009-10-01

Bipolar mania and schizophrenia are recognized as separate disorders but share many commonalities, which raises the question of whether they are the same disorder on different ends of a continuum. The lack of distinct endophenotypes of bipolar mania and schizophrenia has complicated the development of animal models that are specific to these disorders. Exploration is fundamental to survival and is dysregulated in these 2 disorders. Although exploratory behavior in rodents has been widely studied, surprisingly little work has examined this critical function in humans. To quantify the exploratory behavior of individuals with bipolar mania and schizophrenia and to identify distinctive phenotypes of these illnesses. Static group comparison by the use of a novel human open field paradigm, the human Behavioral Pattern Monitor (BPM). Psychiatric hospital. Fifteen patients with bipolar mania and 16 patients with schizophrenia were compared with 26 healthy volunteers in the human BPM. The effects of amphetamine sulfate, the selective dopamine transporter inhibitor GBR12909, and the genetic knockdown of the dopamine transporter were compared with controls in the mouse BPM. The amount of motor activity, spatial patterns of activity, and exploration of novel stimuli were quantified in both the human and mouse BPMs. Patients with bipolar mania demonstrated a unique exploratory pattern, characterized by high motor activity and increased object exploration. Patients with schizophrenia did not show the expected habituation of motor activity. Selective genetic or pharmacologic inhibition of the dopamine transporter matched the mania phenotype better than the effects of amphetamine, which has been the criterion standard for animal models of mania. These findings validate the human open field paradigm and identify defining characteristics of bipolar mania that are distinct from those of schizophrenia. This cross-species study of exploration calls into question an accepted animal model of mania and should help to develop more accurate human and animal models, which are essential to the identification of the neurobiological underpinnings of neuropsychiatric disorders.

A reverse translational study of dysfunctional exploration in psychiatric disorders: from mice to men

PubMed Central

Perry, William; Minassian, Arpi; Paulus, Martin P.; Young, Jared W.; Kincaid, Meegin J.; Ferguson, Eliza J.; Henry, Brook L.; Zhuang, Xiaoxi; Masten, Virginia L.; Sharp, Richard F.; Geyer, Mark A.

2009-01-01

Context Bipolar mania and schizophrenia are recognized as separate disorders but share many commonalities, raising the question of whether they are in fact the same disorder on different ends of a continuum. The lack of distinct endophenotypes of bipolar mania and schizophrenia has complicated the development of animal models that are specific to these disorders. Exploration is fundamental to survival and is dysregulated in these two disorders. Although exploratory behavior in rodents has been widely studied, surprisingly little work has examined this critical function in humans. Objective We used a novel human open field paradigm, the human Behavioral Pattern Monitor (BPM), to quantify exploratory behavior of individuals with bipolar mania and schizophrenia and to identify distinctive phenotypes of these illnesses. Design Static group comparison. Setting Psychiatric hospital. Participants 15 bipolar mania and 16 schizophrenia subjects were compared to 26 healthy volunteers in the human BPM. The effects of amphetamine, the selective dopamine transporter (DAT) inhibitor GBR12909, and genetic knockdown of the DAT were compared to controls in the mouse BPM. Measures The amount of motor activity, spatial patterns of activity, and exploration of novel stimuli were quantified in both the human and mouse BPMs. Results Bipolar manic subjects demonstrated a unique exploratory pattern, characterized by high motor activity and increased object exploration. Schizophrenia subjects did not show the expected habituation of motor activity. Selective genetic or pharmacological inhibition of the DAT matched the mania phenotype better than the “gold standard” model of mania (amphetamine). Conclusion These findings validate the human open field paradigm and identify defining characteristics of bipolar mania that are distinct from schizophrenia. This cross-species study of exploration calls into question an accepted animal model of mania and should help to develop more accurate human and animal models, which are essential to identify neurobiological underpinnings of neuropsychiatric disorders. PMID:19805697

Introduction: The Humanities and the Sciences.

PubMed

Bod, Rens; Kursell, Julia

2015-06-01

The humanities and the sciences have a strongly connected history, yet their histories continue to be written separately. Although the scope of the history of science has undergone a tremendous broadening during the past few decades, scholars of the history of the humanities and the history of science still seem to belong to two separate cultures that have endured through the past century. This Focus section explores what common ground would enable a study of the histories of the humanities and the sciences to investigate their shared epistemic objects, virtues, values, methods, and practices.

Separate Perceptual and Neural Processing of Velocity- and Disparity-Based 3D Motion Signals

PubMed Central

Czuba, Thaddeus B.; Cormack, Lawrence K.; Huk, Alexander C.

2016-01-01

Although the visual system uses both velocity- and disparity-based binocular information for computing 3D motion, it is unknown whether (and how) these two signals interact. We found that these two binocular signals are processed distinctly at the levels of both cortical activity in human MT and perception. In human MT, adaptation to both velocity-based and disparity-based 3D motions demonstrated direction-selective neuroimaging responses. However, when adaptation to one cue was probed using the other cue, there was no evidence of interaction between them (i.e., there was no “cross-cue” adaptation). Analogous psychophysical measurements yielded correspondingly weak cross-cue motion aftereffects (MAEs) in the face of very strong within-cue adaptation. In a direct test of perceptual independence, adapting to opposite 3D directions generated by different binocular cues resulted in simultaneous, superimposed, opposite-direction MAEs. These findings suggest that velocity- and disparity-based 3D motion signals may both flow through area MT but constitute distinct signals and pathways. SIGNIFICANCE STATEMENT Recent human neuroimaging and monkey electrophysiology have revealed 3D motion selectivity in area MT, which is driven by both velocity-based and disparity-based 3D motion signals. However, to elucidate the neural mechanisms by which the brain extracts 3D motion given these binocular signals, it is essential to understand how—or indeed if—these two binocular cues interact. We show that velocity-based and disparity-based signals are mostly separate at the levels of both fMRI responses in area MT and perception. Our findings suggest that the two binocular cues for 3D motion might be processed by separate specialized mechanisms. PMID:27798134

Separate Perceptual and Neural Processing of Velocity- and Disparity-Based 3D Motion Signals.

PubMed

Joo, Sung Jun; Czuba, Thaddeus B; Cormack, Lawrence K; Huk, Alexander C

2016-10-19

Although the visual system uses both velocity- and disparity-based binocular information for computing 3D motion, it is unknown whether (and how) these two signals interact. We found that these two binocular signals are processed distinctly at the levels of both cortical activity in human MT and perception. In human MT, adaptation to both velocity-based and disparity-based 3D motions demonstrated direction-selective neuroimaging responses. However, when adaptation to one cue was probed using the other cue, there was no evidence of interaction between them (i.e., there was no "cross-cue" adaptation). Analogous psychophysical measurements yielded correspondingly weak cross-cue motion aftereffects (MAEs) in the face of very strong within-cue adaptation. In a direct test of perceptual independence, adapting to opposite 3D directions generated by different binocular cues resulted in simultaneous, superimposed, opposite-direction MAEs. These findings suggest that velocity- and disparity-based 3D motion signals may both flow through area MT but constitute distinct signals and pathways. Recent human neuroimaging and monkey electrophysiology have revealed 3D motion selectivity in area MT, which is driven by both velocity-based and disparity-based 3D motion signals. However, to elucidate the neural mechanisms by which the brain extracts 3D motion given these binocular signals, it is essential to understand how-or indeed if-these two binocular cues interact. We show that velocity-based and disparity-based signals are mostly separate at the levels of both fMRI responses in area MT and perception. Our findings suggest that the two binocular cues for 3D motion might be processed by separate specialized mechanisms. Copyright © 2016 the authors 0270-6474/16/3610791-12$15.00/0.

Activity and structure of human acetyl-CoA carboxylase targeted by a specific inhibitor.

PubMed

Jang, SoRi; Gornicki, Piotr; Marjanovic, Jasmina; Bass, Ethan; Lurcotta, Toni; Rodriguez, Pedro; Austin, Jotham; Haselkorn, Robert

2018-05-17

We have studied a series of human acetyl CoA-carboxylase (ACC) 1 and ACC2 proteins with deletions and/or Ser to Ala substitutions of the known phosphorylation sites. In vitro dephosphorylation/phosphorylation experiments reveal a substantial level of phosphorylation of human ACCs produced in insect cells. Our results are consistent with AMPK phosphorylation of Ser 29, Ser 80 , Ser 1,201 and Ser 1,216 . Phosphorylation of the N-terminal regulatory domain decreases ACC1 activity, while phosphorylation of residues in the ACC central domain has no effect. Inhibition of the activity by phosphorylation is significantly more profound at citrate concentrations below 2 mM. Furthermore, deletion of the N-terminal domain facilitates structural changes induced by citrate, including conversion of ACC dimers to linear polymers. We have also identified ACC2 amino acid mutations affecting specific inhibition of the isozyme by compound CD-017-0191. They form two clusters separated by 60-90 Å: one located in the vicinity of the BC active site and the other one in the vicinity of the ACC1 phosphorylation sites in the central domain, suggesting a contribution of the interface of two ACC dimers in the polymer to the inhibitor binding site. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Absence of Detectable Influenza RNA Transmitted via Aerosol during Various Human Respiratory Activities – Experiments from Singapore and Hong Kong

PubMed Central

Cowling, Benjamin J.; Koh, Gerald C.; Chu, Daniel; Heilbronn, Cherie; Lloyd, Belinda; Pantelic, Jovan; Nicolle, Andre D.; Klettner, Christian A.; Peiris, J. S. Malik; Sekhar, Chandra; Cheong, David K. W.; Tham, Kwok Wai; Koay, Evelyn S. C.; Tsui, Wendy; Kwong, Alfred; Chan, Kitty; Li, Yuguo

2014-01-01

Two independent studies by two separate research teams (from Hong Kong and Singapore) failed to detect any influenza RNA landing on, or inhaled by, a life-like, human manikin target, after exposure to naturally influenza-infected volunteers. For the Hong Kong experiments, 9 influenza-infected volunteers were recruited to breathe, talk/count and cough, from 0.1 m and 0.5 m distance, onto a mouth-breathing manikin. Aerosolised droplets exhaled from the volunteers and entering the manikin’s mouth were collected with PTFE filters and an aerosol sampler, in separate experiments. Virus detection was performed using an in-house influenza RNA reverse-transcription polymerase chain reaction (RT-PCR) assay. No influenza RNA was detected from any of the PTFE filters or air samples. For the Singapore experiments, 6 influenza-infected volunteers were asked to breathe (nasal/mouth breathing), talk (counting in English/second language), cough (from 1 m/0.1 m away) and laugh, onto a thermal, breathing manikin. The manikin’s face was swabbed at specific points (around both eyes, the nostrils and the mouth) before and after exposure to each of these respiratory activities, and was cleaned between each activity with medical grade alcohol swabs. Shadowgraph imaging was used to record the generation of these respiratory aerosols from the infected volunteers and their impact onto the target manikin. No influenza RNA was detected from any of these swabs with either team’s in-house diagnostic influenza assays. All the influenza-infected volunteers had diagnostic swabs taken at recruitment that confirmed influenza (A/H1, A/H3 or B) infection with high viral loads, ranging from 105-108 copies/mL (Hong Kong volunteers/assay) and 104–107 copies/mL influenza viral RNA (Singapore volunteers/assay). These findings suggest that influenza RNA may not be readily transmitted from naturally-infected human source to susceptible recipients via these natural respiratory activities, within these exposure time-frames. Various reasons are discussed in an attempt to explain these findings. PMID:25208000

Two Degrees of Separation: Abrupt Climate Change and the Adverse Impact to US National Security

DTIC Science & Technology

2009-04-01

concentrations of CO2 , CH4 and N2O have increased markedly as a result of human activities since 1750 and now far exceed pre-industrial values...determined from ice cores spanning many thousands of years. The atmospheric concentrations of CO2 and CH4 in 2005 exceed by far the natural range over the...last 650,000 years. Global increases in CO2 concentrations are due primarily to fossil fuel use, with land-use change providing another significant

Chemistry and Biochemistry of Dietary Polyphenols

PubMed Central

Tsao, Rong

2010-01-01

Polyphenols are the biggest group of phytochemicals, and many of them have been found in plant-based foods. Polyphenol-rich diets have been linked to many health benefits. This paper is intended to review the chemistry and biochemistry of polyphenols as related to classification, extraction, separation and analytical methods, their occurrence and biosynthesis in plants, and the biological activities and implications in human health. The discussions are focused on important and most recent advances in the above aspects, and challenges are identified for future research. PMID:22254006

Synthesis and pharmacological characterization of beta2-adrenergic agonist enantiomers: zilpaterol.

PubMed

Kern, Christopher; Meyer, Thorsten; Droux, Serge; Schollmeyer, Dieter; Miculka, Christian

2009-03-26

The beta-adrenergic agonist 1 (zilpaterol) is used as production enhancer in cattle. Binding experiments of separated enantiomers on recombinant human beta(2)-adrenergic and mu-opioid receptors and functional studies showed that the (-)-1 enantiomer accounts for essentially all the beta(2)-adrenergic agonist activity and that it exhibits less affinity toward the mu-opioid receptor than (+)-1, which is a mu-opioid receptor antagonist. X-ray crystallography revealed the absolute configuration of (-)-1 to be 6R,7R.

Chemical Carcinogen-Induced Changes in tRNA Metabolism in Human Cells

DTIC Science & Technology

1984-11-20

uptake Chart 7 by POD was not affected by concurrent treatment with 0.1 mM quercetin (Chart 7). Epidermal growth factor (100 nM) also had no affect on...Therefore, we examined the affect on queuine uptake of quercetin , a flavanoid inhibitor of protein kinase C which binds to a site separate from the...phorbol ester binding site (12). Quercetin did not relieve the POO-effected inhibition of rQT3 uptake.. Although some residual activity of membrane bound

Use of vancomycin silica stationary phase in packed capillary electrochromatography. II. Enantiomer separation of venlafaxine and O-desmethylvenlafaxine in human plasma.

PubMed

Fanali, S; Rudaz, S; Veuthey, J L; Desiderio, C

2001-06-01

A capillary electrochromatography method, using vancomycin chiral stationary phase packed capillary, was optimized for the simultaneous chiral separation of the antidepressant drug venlafaxine and its main active metabolite O-desmethylvenlafaxine. Simultaneous baseline enantiomeric separation of the two compounds was obtained using a mobile phase composed of 100 mM ammonium acetate buffer pH 6/water/acetonitrile (5:5:90, v/v). The electrokinetic injection for sample introduction provided a limit of quantitation for both the compounds of 0.05 microg/ml racemate concentration suitable for the analysis of venlafaxine and metabolite in biological samples. The acetonitrile mobile phase concentration was found to modulate the analytes elution times, the enantiomeric resolution and the efficiency of the separation. The column was tested for repeatability and linearity showing RSD values (%) in the range of 0.13-0.24, 2.47-3.66 and 1.35-2.50 for migration time, sample/internal standard peak area ratio and enantiomeric resolution, respectively and correlation coefficients higher than 0.9990. The method was applied to the analysis of clinical samples of patients under depression therapy showing a stereoselective metabolism for venlafaxine.

Effect of a streptococcal preparation (OK432) on natural killer activity of tumour-associated lymphoid cells in human ovarian carcinoma and on lysis of fresh ovarian tumour cells.

PubMed Central

Colotta, F.; Rambaldi, A.; Colombo, N.; Tabacchi, L.; Introna, M.; Mantovani, A.

1983-01-01

The streptococcal preparation OK432 was studied for its effects on natural killer (NK) activity of peripheral blood lymphocytes (PBL) from normal donors and from ovarian cancer patients, and of tumour-associated lymphocytes (TAL) from peritoneal effusions. OK432 augmented NK activity against the susceptible K562 line and induced killing of the relatively resistant Raji line. Freshly isolated ovarian carcinoma cells were relatively resistant to killing by unstimulated PBL and TAL. OK432 induced significant, though low, levels of cytotoxicity against 51Cr-labelled ovarian carcinoma cells. Augmentation of killing of fresh tumour cells by OK432 was best observed in a 20 h assay and both autologous and allogeneic targets were lysed. PBL were separated on discontinuous Percoll gradients. Unstimulated and OK432-boosted activity were enriched in the lower density fractions where large granular lymphocytes (LGL) and activity against K562 were found. Thus, OK432 augments NK activity of PBL and TAL in human ovarian carcinomas and induces low, but significant, levels of killing of fresh tumour cells. Effector cells involved in killing of fresh ovarian tumours copurify with LGL on discontinuous gradients of Percoll. PMID:6626452

The Effect of Silver Carp Skin-Derived Peptides on the Activities of VEGF and Hsp70.1 Gene Transcription Promoters.

PubMed

Wojtkowiak, Diana; Piechowicz, Janina; Grzenkowicz-Wydra, Jolanta; Wosiński, Stanisław; Dominiak, Marzena; Hadzik, Jakub; Frydrychowski, Andrzej F

2016-01-01

Studies conducted on human cell culture models have demonstrated that collagen-derived peptides can exert a beneficial effect in medicine. However, all these studies were conducted using animal collagen samples, most often originating from bovine or porcine skin. Currently attempts are being made to replace animal collagen with fish collagen. The aim of the study was to compare the effect of silver carp skin-derived peptide extract on the transcriptional activities of human VEGF and hsp70.1 gene promoters inserted into the plasmids with secreted alkaline phosphatase as a reporter gene. Changes in the activity of the promoters were investigated using a HEK293FT cell line transfected with pVEGF-SEAP or pHsp70-SEAP. The cells were cultured in dishes containing peptides separated using reverse-phase high performance liquid chromatography. The study demonstrated that the silver carp skin-derived peptide extract exerts both an inhibitory effect on the VEGF gene promoter and activating effect on the hsp70.1 gene promoter. Higher biological activity was recorded in the case of a freshly prepared peptide extract compared to one stored at 4°C for three months. The silver carp skin-derived collagen peptides influence VEGF and hsp70.1 gene promoters' transcriptional activity.

Human leukocytic pyrogen: purification and development of a radioimmunoassay.

PubMed

Dinarello, C A; Renfer, L; Wolff, S M

1977-10-01

Leukocytic pyrogen is a small endogenous protein that mediates fever. Because of the limitations of bioassays, circulating leukocytic pyrogen has not been demonstrated during fever in humans. The pyrogen was produced in vitro after phagocytosis of staphylococci by blood monocytes. Antibody against the pyrogen was obtained from rabbits immunized with leukocytic pyrogen and the antiserum was purified by solid-phase immunoadsorbants. Purified antibody to the pyrogen was attached to activated Sepharose 4B and used in conjunction with gel filtration to purify the pyrogen. The pyrogen was labeled with 125I and further purified by gel filtration and ion-exchange chromatography. The final preparation of 125I-labeled pyrogen demonstrated a homogeneous band during isoelectric focusing and other separation procedures. With antibody to pyrogen attached to Sepharose, less than 0.1 of a rabbit pyrogenic dose of human leukocytic pyrogen inhibited the binding of 125I-labeled pyrogen to this immunoadsorbant, and this inhibition was not affected by the presence of human serum. Thus, a radioimmunoassay for human leukocytic pyrogen has been developed that may be used to detect circulating pyrogen during fever in humans.

Strategic Resource Allocation in the Human Brain Supports Cognitive Coordination of Object and Spatial Working Memory

PubMed Central

Jackson, Margaret C; Morgan, Helen M; Shapiro, Kimron L; Mohr, Harald; Linden, David EJ

2011-01-01

The ability to integrate different types of information (e.g., object identity and spatial orientation) and maintain or manipulate them concurrently in working memory (WM) facilitates the flow of ongoing tasks and is essential for normal human cognition. Research shows that object and spatial information is maintained and manipulated in WM via separate pathways in the brain (object/ventral versus spatial/dorsal). How does the human brain coordinate the activity of different specialized systems to conjoin different types of information? Here we used functional magnetic resonance imaging to investigate conjunction- versus single-task manipulation of object (compute average color blend) and spatial (compute intermediate angle) information in WM. Object WM was associated with ventral (inferior frontal gyrus, occipital cortex), and spatial WM with dorsal (parietal cortex, superior frontal, and temporal sulci) regions. Conjoined object/spatial WM resulted in intermediate activity in these specialized areas, but greater activity in different prefrontal and parietal areas. Unique to our study, we found lower temporo-occipital activity and greater deactivation in temporal and medial prefrontal cortices for conjunction- versus single-tasks. Using structural equation modeling, we derived a conjunction-task connectivity model that comprises a frontoparietal network with a bidirectional DLPFC-VLPFC connection, and a direct parietal-extrastriate pathway. We suggest that these activation/deactivation patterns reflect efficient resource allocation throughout the brain and propose a new extended version of the biased competition model of WM. Hum Brain Mapp, 2011. © 2010 Wiley-Liss, Inc. PMID:20715083

Separation of Carbon Monoxide and Carbon Dioxide for Mars ISRU

NASA Technical Reports Server (NTRS)

Walton, Krista S.; LeVan, M. Douglas

2004-01-01

The atmosphere of Mars has many resources that can be processed to produce things such as oxygen, fuel, buffer gas, and water for support of human exploration missions. Successful manipulation of these resources is crucial for safe, cost-effective, and self-sufficient long-term human exploration of Mars. In our research, we are developing enabling technologies that require fundamental knowledge of adsorptive gas storage and separation processes. In particular, we are designing and constructing an innovative, low mass, low power separation device to recover carbon dioxide and carbon monoxide for Mars ISRU (in-situ resource utilization). The technology has broad implications for gas storage and separations for gas-solid systems that are ideally suited for reduced gravitational environments. This paper describes our separation process design and experimental procedures and reports results for the separation of CO2 and CO by a four-step adsorption cycle.

International Space Station Common Cabin Air Assembly Water Separator On-Orbit Operation, Failure, and Redesign

NASA Technical Reports Server (NTRS)

Balistreri, Steven F., Jr.; Shaw, Laura A.; Laliberte, Yvon

2010-01-01

The ability to control the temperature and humidity of an environment or habitat is critical for human survival. These factors are important to maintaining human health and comfort, as well as maintaining mechanical and electrical equipment in good working order to support the human and to accomplish mission objectives. The temperature and humidity of the International Space Station (ISS) United States On-orbit Segment (USOS) cabin air is controlled by the Common Cabin Air Assembly (CCAA). The CCAA consists of a fan, a condensing heat exchanger (CHX), an air/water separator, temperature and liquid sensors, and electrical controlling hardware and software. The Water Separator (WS) pulls in air and water from the CHX, and centrifugally separates the mixture, sending the water to the condensate bus and the air back into the CHX outlet airstream. Two distinct early failures of the CCAA Water Separator in the Quest Airlock forced operational changes and brought about the re-design of the Water Separator to improve the useful life via modification kits. The on-orbit operational environment of the Airlock presented challenges that were not foreseen with the original design of the Water Separator. Operational changes were instituted to prolong the life of the third installed WS, while waiting for newly designed Water Separators to be delivered on-orbit. The modification kit design involved several different components of the Water Separator, including the innovative use of a fabrication technique to build the impellers used in Water Separators out of titanium instead of aluminum. The technique allowed for the cost effective production of the low quantity build. This paper will describe the failures of the Water Separators in the Quest Airlock, the operational constraints that were implemented to prolong the life of the installed Water Separators throughout the USOS, and the innovative re-design of the CCAA Water Separator.

[Construction, expression and characterization of the fusion gene of super-antigen SEA and single chain Fv of the ND-1 monoclonal antibody against human colorectal cancer].

PubMed

Chen, Hang; Li, Li; Fang, Jin

2012-04-01

To construct and express the recombinant ND-1-scFv/SEA, a fusion protein of superantigen (staphylococcal enterotoxinA, SEA) and single-chain variable fragment of monoclonal antibody ND-1 against human clolorectal carcinoma, and to enhance the targeted killing effect of SEA. The expression of the fusion protein was induced in E.coli M15 by IPTG. Ni-NTA resin affinity chromatography was used to separate and purify the expressed product. The specific binding activity of the purified ND-1-scFv/SEA protein was examined by indirect immunofluorescence assay and the targeted-cytotoxicity was determined using MTT assay. The expressing vector of fusion gene ND-1scFv/SEA was constructed successfully. ND-1-scFv/SEA protein retained a high binding affinity to antigen-positive human colorectal cancer cell CCL-187 and had a stronger capability to activate PBMC and kill the target cells compared to SEA alone, with a killing rate of 91% at 4 μg/mL. ND-1-scFv/SEA fusion protein could specifically target colorectal cancer cell, enhance the activity of kill tumor cell and has potential applications in the targeted therapy of colorectal cancer.

Active Interpersonal Touch Gives Rise to the Social Softness Illusion

PubMed Central

Gentsch, Antje; Panagiotopoulou, Elena; Fotopoulou, Aikaterini

2015-01-01

Summary Social touch plays a powerful role in human life, with important physical and mental health benefits in development and adulthood. Touch is central in building the foundations of social interaction, attachment, and cognition [1–5], and early, social touch has unique, beneficial neurophysiological and epigenetic effects [6–9]. The recent discovery of a separate neurophysiological system for affectively laden touch in humans has further kindled scientific interest in the area [10, 11]. Remarkably, however, little is known about what motivates and sustains the human tendency to touch others in a pro-social manner. Given the importance of social touch, we hypothesized that active stroking elicits more sensory pleasure when touching others’ skin than when touching one’s own skin. In a set of six experiments (total N = 133) we found that healthy participants, mostly tested in pairs to account for any objective differences in skin softness, consistently judged another’s skin as feeling softer and smoother than their own skin. We further found that this softness illusion appeared selectively when the touch activated a neurophysiological system for affective touch in the receiver. We conclude that this sensory illusion underlies a novel, bodily mechanism of socio-affective bonding and enhances our motivation to touch others. PMID:26365257

Chimpanzees' context-dependent tool use provides evidence for separable representations of hand and tool even during active use within peripersonal space.

PubMed

Povinelli, Daniel J; Reaux, James E; Frey, Scott H

2010-01-01

Considerable attention has been devoted to behaviors in which tools are used to perform actions in extrapersonal space by extending the reach. Evidence suggests that these behaviors result in an expansion of the body schema and peripersonal space. However, humans often use tools to perform tasks within peripersonal space that cannot be accomplished with the hands. In some of these instances (e.g., cooking), a tool is used as a substitute for the hand in order to pursue actions that would otherwise be hazardous. These behaviors suggest that even during the active use of tools, we maintain non-isomorphic representations that distinguish between our hands and handheld tools. Understanding whether such representations are a human specialization is of potentially great relevance to understand the evolutionary history of technological behaviors including the controlled use of fire. We tested six captive adult chimpanzees to determine whether they would elect to use a tool, rather than their hands, when acting in potentially hazardous vs. nonhazardous circumstances located within reach. Their behavior suggests that, like humans, chimpanzees represent the distinction between the hand vs. tool even during active use. We discuss the implications of this evidence for our understanding of tool use and its evolution.

Temporal coherence for pure tones in budgerigars (Melopsittacus undulatus) and humans (Homo sapiens).

PubMed

Neilans, Erikson G; Dent, Micheal L

2015-02-01

Auditory scene analysis has been suggested as a universal process that exists across all animals. Relative to humans, however, little work has been devoted to how animals perceptually isolate different sound sources. Frequency separation of sounds is arguably the most common parameter studied in auditory streaming, but it is not the only factor contributing to how the auditory scene is perceived. Researchers have found that in humans, even at large frequency separations, synchronous tones are heard as a single auditory stream, whereas asynchronous tones with the same frequency separations are perceived as 2 distinct sounds. These findings demonstrate how both the timing and frequency separation of sounds are important for auditory scene analysis. It is unclear how animals, such as budgerigars (Melopsittacus undulatus), perceive synchronous and asynchronous sounds. In this study, budgerigars and humans (Homo sapiens) were tested on their perception of synchronous, asynchronous, and partially overlapping pure tones using the same psychophysical procedures. Species differences were found between budgerigars and humans in how partially overlapping sounds were perceived, with budgerigars more likely to segregate overlapping sounds and humans more apt to fuse the 2 sounds together. The results also illustrated that temporal cues are particularly important for stream segregation of overlapping sounds. Lastly, budgerigars were found to segregate partially overlapping sounds in a manner predicted by computational models of streaming, whereas humans were not. PsycINFO Database Record (c) 2015 APA, all rights reserved.

FDG-PET detects nonuniform muscle activity in the lower body during human gait.

PubMed

Kindred, John H; Ketelhut, Nathaniel B; Benson, John-Michael; Rudroff, Thorsten

2016-11-01

Nonuniform muscle activity has been partially explained by anatomically defined neuromuscular compartments. The purpose of this study was to investigate the uniformity of skeletal muscle activity during walking. Eight participants walked at a self-selected speed, and muscle activity was quantified using [ 18 F]-fluorodeoxyglucose positron emission tomography imaging. Seventeen muscles were divided into 10 equal length sections, and within muscle activity was compared. Nonuniform activity was detected in 12 of 17 muscles (ƒ > 4.074; P < 0.046), which included both uni- and multi-articular muscles. Greater proximal activity was detected in 6 muscles (P < 0.049), and greater distal versus medial activity was found in the iliopsoas (P < 0.042). Nonuniform muscle activity is likely related to recruitment of motor units located within separate neuromuscular compartments. These findings indicate that neuromuscular compartments are recruited selectively to allow for efficient energy transfer, and these patterns may be task-dependent. Muscle Nerve 54: 959-966, 2016. © 2016 Wiley Periodicals, Inc.

Phenylbutyrate induces LL-37-dependent autophagy and intracellular killing of Mycobacterium tuberculosis in human macrophages

PubMed Central

Rekha, Rokeya Sultana; Rao Muvva, SSV Jagadeeswara; Wan, Min; Raqib, Rubhana; Bergman, Peter; Brighenti, Susanna; Gudmundsson, Gudmundur H; Agerberth, Birgitta

2015-01-01

LL-37 is a human antimicrobial peptide (AMP) of the cathelicidin family with multiple activities including a mediator of vitamin D-induced autophagy in human macrophages, resulting in intracellular killing of Mycobacterium tuberculosis (Mtb). In a previous trial in healthy volunteers, we have shown that LL-37 expression and subsequent Mtb-killing can be further enhanced by 4-phenylbutyrate (PBA), also an inducer of LL-37 expression. Here, we explore a potential mechanism(s) behind PBA and LL-37-induced autophagy and intracellular killing of Mtb. Mtb infection of macrophages downregulated the expression of both the CAMP transcript and LL-37 peptide as well as certain autophagy-related genes (BECN1 and ATG5) at both the mRNA and protein levels. In addition, activation of LC3-II in primary macrophages and THP-1 cells was not detected. PBA and the active form of vitamin D3 (1,25[OH]2D3), separately or particularly in combination, were able to overcome Mtb-induced suppression of LL-37 expression. Notably, reactivation of autophagy occurred by stimulation of macrophages with PBA and promoted colocalization of LL-37 and LC3-II in autophagosomes. Importantly, PBA treatment failed to induce autophagy in Mtb-infected THP-1 cells, when the expression of LL-37 was silenced. However, PBA-induced autophagy was restored when the LL-37 knockdown cells were supplemented with synthetic LL-37. Interestingly, we have found that LL-37-induced autophagy was mediated via P2RX7 receptor followed by enhanced cytosolic free Ca2+, and activation of AMPK and PtdIns3K pathways. Altogether, these results suggest a novel activity for PBA as an inducer of autophagy, which is LL-37-dependent and promotes intracellular killing of Mtb in human macrophages. PMID:26218841

Sp1 and Sp3 Are the Transcription Activators of Human ek1 Promoter in TSA-Treated Human Colon Carcinoma Cells.

PubMed

Kuan, Chee Sian; See Too, Wei Cun; Few, Ling Ling

2016-01-01

Ethanolamine kinase (EK) catalyzes the phosphorylation of ethanolamine, the first step in the CDP-ethanolamine pathway for the biosynthesis of phosphatidylethanolamine (PE). Human EK exists as EK1, EK2α and EK2β isoforms, encoded by two separate genes, named ek1 and ek2. EK activity is stimulated by carcinogens and oncogenes, suggesting the involvement of EK in carcinogenesis. Currently, little is known about EK transcriptional regulation by endogenous or exogenous signals, and the ek gene promoter has never been studied. In this report, we mapped the important regulatory regions in the human ek1 promoter. 5' deletion analysis and site-directed mutagenesis identified a Sp site at position (-40/-31) that was essential for the basal transcription of this gene. Treatment of HCT116 cells with trichostatin A (TSA), a histone deacetylase inhibitor, significantly upregulated the ek1 promoter activity through the Sp(-40/-31) site and increased the endogenous expression of ek1. Chromatin immunoprecipitation assay revealed that TSA increased the binding of Sp1, Sp3 and RNA polymerase II to the ek1 promoter in HCT116 cells. The effect of TSA on ek1 promoter activity was cell-line specific as TSA treatment did not affect ek1 promoter activity in HepG2 cells. In conclusion, we showed that Sp1 and Sp3 are not only essential for the basal transcription of the ek1 gene, their accessibility to the target site on the ek1 promoter is regulated by histone protein modification in a cell line dependent manner.

Magnetic-Activated Cell Sorting for the Fast and Efficient Separation of Human and Rodent Schwann Cells from Mixed Cell Populations.

PubMed

Ravelo, Kristine M; Andersen, Natalia D; Monje, Paula V

2018-01-01

To date, magnetic-activated cell sorting (MACS) remains a powerful method to isolate distinct cell populations based on differential cell surface labeling. Optimized direct and indirect MACS protocols for cell immunolabeling are presented here as methods to divest Schwann cell (SC) cultures of contaminating cells (specifically, fibroblast cells) and isolate SC populations at different stages of differentiation. This chapter describes (1) the preparation of single-cell suspensions from established human and rat SC cultures, (2) the design and application of cell selection strategies using SC-specific (p75 NGFR , O4, and O1) and fibroblast-specific (Thy-1) markers, and (3) the characterization of both the pre- and post-sorting cell populations. A simple protocol for the growth of hybridoma cell cultures as a source of monoclonal antibodies for cell surface immunolabeling of SCs and fibroblasts is provided as a cost-effective alternative for commercially available products. These steps allow for the timely and efficient recovery of purified SC populations without compromising the viability and biological activity of the cells.

S-Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP-glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen

PubMed Central

Bowalgaha, Kushari; Elliot, David J; Mackenzie, Peter I; Knights, Kathleen M; Swedmark, Stellan; Miners, John O

2005-01-01

Aims To characterize the kinetics of S-naproxen (‘naproxen’) acyl glucuronidation and desmethylnaproxen acyl and phenolic glucuronidation by human liver microsomes and identify the human UGT isoform(s) catalysing these reactions. Methods Naproxen and desmethylnaproxen glucuronidation were investigated using microsomes from six and five livers, respectively. Human recombinant UGTs were screened for activity towards naproxen and desmethylnaproxen. Where significant activity was observed, kinetic parameters were determined. Naproxen and desmethylnaproxen glucuronides were measured by separate high-performance liquid chromatography methods. Results Naproxen acyl glucuronidation by human liver microsomes followed biphasic kinetics. Mean apparent Km values (±SD, with 95% confidence interval in parentheses) for the high- and low-affinity components were 29 ± 13 µm (16, 43) and 473 ± 108 µm (359, 587), respectively. UGT 1A1, 1A3, 1A6, 1A7, 1A8, 1A9, 1A10 and 2B7 glucuronidated naproxen. UGT2B7 exhibited an apparent Km (72 µm) of the same order as the high-affinity human liver microsomal activity, which was inhibited by the UGT2B7 selective ‘probe’ fluconazole. Although data for desmethylnaproxen phenolic glucuronidation by human liver microsomes were generally adequately fitted to either the single- or two-enzyme Michaelis–Menten equation, model fitting was inconclusive for desmethylnaproxen acyl glucuronidation. UGT 1A1, 1A7, 1A9 and 1A10 catalysed both the phenolic and acyl glucuronidation of desmethylnaproxen, while UGT 1A3, 1A6 and 2B7 formed only the acyl glucuronide. Atypical glucuronidation kinetics were variably observed for naproxen and desmethylnaproxen glucuronidation by the recombinant UGTs. Conclusion UGT2B7 is responsible for human hepatic naproxen acyl glucuronidation, which is the primary elimination pathway for this drug. PMID:16187975

The role of oxytocin in relationships between dogs and humans and potential applications for the treatment of separation anxiety in dogs.

PubMed

Thielke, Lauren E; Udell, Monique A R

2017-02-01

The hormone oxytocin plays an important role in attachment formation and bonding between humans and domestic dogs. Recent research has led to increased interest in potential applications for intranasal oxytocin to aid with the treatment of psychological disorders in humans. While a few studies have explored the effects of intranasally administered oxytocin on social cognition and social bonding in dogs, alternative applications have not yet been explored for the treatment of behavioural problems in this species. One potentially important application for intranasal oxytocin in dogs could be the treatment of separation anxiety, a common attachment disorder in dogs. Here we provide an overview of what is known about the role of oxytocin in the human-dog bond and canine separation anxiety, and discuss considerations for future research looking to integrate oxytocin into behavioural treatment based on recent findings from both the human and dog literature. © 2015 Cambridge Philosophical Society.

Egocentric daily activity recognition via multitask clustering.

PubMed

Yan, Yan; Ricci, Elisa; Liu, Gaowen; Sebe, Nicu

2015-10-01

Recognizing human activities from videos is a fundamental research problem in computer vision. Recently, there has been a growing interest in analyzing human behavior from data collected with wearable cameras. First-person cameras continuously record several hours of their wearers' life. To cope with this vast amount of unlabeled and heterogeneous data, novel algorithmic solutions are required. In this paper, we propose a multitask clustering framework for activity of daily living analysis from visual data gathered from wearable cameras. Our intuition is that, even if the data are not annotated, it is possible to exploit the fact that the tasks of recognizing everyday activities of multiple individuals are related, since typically people perform the same actions in similar environments, e.g., people working in an office often read and write documents). In our framework, rather than clustering data from different users separately, we propose to look for clustering partitions which are coherent among related tasks. In particular, two novel multitask clustering algorithms, derived from a common optimization problem, are introduced. Our experimental evaluation, conducted both on synthetic data and on publicly available first-person vision data sets, shows that the proposed approach outperforms several single-task and multitask learning methods.

The human apolipoprotein AV gene is regulated by peroxisome proliferator-activated receptor-alpha and contains a novel farnesoid X-activated receptor response element.

PubMed

Prieur, Xavier; Coste, Herve; Rodriguez, Joan C

2003-07-11

The newly identified apolipoprotein AV (apoAV) gene is a key player in determining plasma triglyceride concentrations. Because hypertriglyceridemia is a major independent risk factor in coronary artery disease, the understanding of the regulation of the expression of this gene is of considerable importance. We presently characterize the structure, the transcription start site, and the promoter of the human apoAV gene. Since the peroxisome proliferator-activated receptor-alpha (PPARalpha) and the farnesoid X-activated receptor (FXR) have been shown to modulate the expression of genes involved in triglyceride metabolism, we evaluated the potential role of these nuclear receptors in the regulation of apoAV transcription. Bile acids and FXR induced the apoAV gene promoter activity. 5'-Deletion, mutagenesis, and gel shift analysis identified a heretofore unknown element at positions -103/-84 consisting of an inverted repeat of two consensus receptor-binding hexads separated by 8 nucleotides (IR8), which was required for the response to bile acid-activated FXR. The isolated IR8 element conferred FXR responsiveness on a heterologous promoter. On the other hand, in apoAV-expressing human hepatic Hep3B cells, transfection of PPARalpha specifically enhanced apoAV promoter activity. By deletion, site-directed mutagenesis, and binding analysis, a PPARalpha response element located 271 bp upstream of the transcription start site was identified. Finally, treatment with a specific PPARalpha activator led to a significant induction of apoAV mRNA expression in hepatocytes. The identification of apoAV as a PPARalpha target gene has major implications with respect to mechanisms whereby pharmacological PPARalpha agonists may exert their beneficial hypotriglyceridemic actions.

Memory in the making: localized brain activation related to song learning in young songbirds

PubMed Central

Gobes, Sharon M. H.; Zandbergen, Matthijs A.; Bolhuis, Johan J.

2010-01-01

Songbird males learn to sing their songs from an adult ‘tutor’ early in life, much like human infants learn to speak. Similar to humans, in the songbird brain there are separate neural substrates for vocal production and for auditory memory. In adult songbirds, the caudal pallium, the avian equivalent of the auditory association cortex, has been proposed to contain the neural substrate of tutor song memory, while the song system is involved in song production as well as sensorimotor learning. If this hypothesis is correct, there should be neuronal activation in the caudal pallium, and not in the song system, while the young bird is hearing the tutor song. We found increased song-induced molecular neuronal activation, measured as the expression of an immediate early gene, in the caudal pallium of juvenile zebra finch males that were in the process of learning to sing their songs. No such activation was found in the song system. Molecular neuronal activation was significantly greater in response to tutor song than to novel song or silence in the medial part of the caudomedial nidopallium (NCM). In the caudomedial mesopallium, there was significantly greater molecular neuronal activation in response to tutor song than to silence. In addition, in the NCM there was a significant positive correlation between spontaneous molecular neuronal activation and the strength of song learning during sleep. These results suggest that the caudal pallium contains the neural substrate for tutor song memory, which is activated during sleep when the young bird is in the process of learning its song. The findings provide insight into the formation of auditory memories that guide vocal production learning, a process fundamental for human speech acquisition. PMID:20534608

Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma.

PubMed

Stenland, Christopher J; Lee, Douglas C; Brown, Paul; Petteway, Stephen R; Rubenstein, Richard

2002-11-01

Therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (TSE) transmission. Previously, hamster-adapted scrapie was used as a model agent to assess TSE clearance in purification steps leading to the isolation of biopharmaceutical proteins. The current study investigated the validity of hamster scrapie as a model for human TSE clearance studies. The partitioning of the pathogenic forms of the prion protein associated with human variant CJD (PrP(vCJD)), human sporadic CJD (PrP(sCJD)) and Gerstmann-Sträussler-Scheinker (PrP(GSS)) syndrome was compared to the partitioning of hamster scrapie (PrP(Sc)) in three plasma protein purification steps. Sheep scrapie (PrP(Sc)) was similarly evaluated. The starting materials for three plasma protein purification steps, cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation, were spiked with brain homogenates containing human PrP(vCJD), human PrP(sCJD), human PrP(GSS), sheep PrP(Sc), and hamster 263K PrP(Sc). The partitioning of the pathogenic form of the PrP was analyzed. Clearance of the pathogenic form of the PrP was measured relative to the effluent fraction. Regardless of the source of the pathogenic prion, clearance was similar to hamster PrP(Sc). A nominal amount of clearance (approx., 1 log), an intermediate amount of clearance (approx., 2 log), and a substantial amount of clearance (> or = 3 log) were observed for the cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation steps, respectively. In the latter step, no PrP was detected in the effluents. These data demonstrate that human prions, including vCJD prions, can be removed during the purification of human therapeutic proteins and indicate that partitioning of human prions is similar to that observed in the hamster scrapie model.

Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models

PubMed Central

Wen, Li; Voronina, Svetlana; Javed, Muhammad A.; Awais, Muhammad; Szatmary, Peter; Latawiec, Diane; Chvanov, Michael; Collier, David; Huang, Wei; Barrett, John; Begg, Malcolm; Stauderman, Ken; Roos, Jack; Grigoryev, Sergey; Ramos, Stephanie; Rogers, Evan; Whitten, Jeff; Velicelebi, Gonul; Dunn, Michael; Tepikin, Alexei V.; Criddle, David N.; Sutton, Robert

2015-01-01

Background & Aims Sustained activation of the cytosolic calcium concentration induces injury to pancreatic acinar cells and necrosis. The calcium release–activated calcium modulator ORAI1 is the most abundant Ca2+ entry channel in pancreatic acinar cells; it sustains calcium overload in mice exposed to toxins that induce pancreatitis. We investigated the roles of ORAI1 in pancreatic acinar cell injury and the development of acute pancreatitis in mice. Methods Mouse and human acinar cells, as well as HEK 293 cells transfected to express human ORAI1 with human stromal interaction molecule 1, were hyperstimulated or incubated with human bile acid, thapsigargin, or cyclopiazonic acid to induce calcium entry. GSK-7975A or CM_128 were added to some cells, which were analyzed by confocal and video microscopy and patch clamp recordings. Acute pancreatitis was induced in C57BL/6J mice by ductal injection of taurolithocholic acid 3-sulfate or intravenous' administration of cerulein or ethanol and palmitoleic acid. Some mice then were given GSK-7975A or CM_128, which inhibit ORAI1, at different time points to assess local and systemic effects. Results GSK-7975A and CM_128 each separately inhibited toxin-induced activation of ORAI1 and/or activation of Ca2+ currents after Ca2+ release, in a concentration-dependent manner, in mouse and human pancreatic acinar cells (inhibition >90% of the levels observed in control cells). The ORAI1 inhibitors also prevented activation of the necrotic cell death pathway in mouse and human pancreatic acinar cells. GSK-7975A and CM_128 each inhibited all local and systemic features of acute pancreatitis in all 3 models, in dose- and time-dependent manners. The agents were significantly more effective, in a range of parameters, when given at 1 vs 6 hours after induction of pancreatitis. Conclusions Cytosolic calcium overload, mediated via ORAI1, contributes to the pathogenesis of acute pancreatitis. ORAI1 inhibitors might be developed for the treatment of patients with pancreatitis. PMID:25917787

The effect of stem cell from human exfoliated deciduous teeth on T lymphocyte proliferation

PubMed Central

Alipour, Razieh; Adib, Minoo; Hashemi-Beni, Batool; Sadeghi, Farzaneh

2014-01-01

Background: Mesenchymal stem cells (MSC), a specific type of adult tissue stem cell; have the immunosuppressive effects that make them valuable targets for regenerative medicine and treatment of many human illnesses. Hence, MSC have been the subject of numerous studies. The classical source of MSC is adult bone marrow (BM). Due to many shortcomings of harvesting MSC from BM, finding the alternative sources for MSC is an urgent. Stem cells from human exfoliated deciduous teeth (SHED) are relative new MSC populations that fulfill these criteria but their potential immunosuppressive effect has not been studied enough yet. Thus, in this work the effect of SHED on the proliferation of in vitro activated T lymphocytes were explored. Materials and Methods: In this study, both mitogen and alloantigen activated T cells were cultured in the presence of different numbers of SHED. In some co-cultures, activated T cells were in direct contact to MSCs and in other co-cultures; they were separated from SHED by a permeable membrane. In all co-cultures, the proliferation of T cells was measured by ELISA Bromodeoxyuridine proliferation assay. Results: In general, our results showed that SHED significantly suppress the proliferation of activated T cells in a dose-dependent manner. Moreover, the suppression was slightly stronger when MSCs were in physical contact to activated T cells. Conclusion: This study showed that SHED likewise other MSC populations can suppress the activation of T lymphocytes, which can be used instead of BM derived MSCs in many investigational and clinical applications. PMID:25337532

Brain regions with mirror properties: a meta-analysis of 125 human fMRI studies.

PubMed

Molenberghs, Pascal; Cunnington, Ross; Mattingley, Jason B

2012-01-01

Mirror neurons in macaque area F5 fire when an animal performs an action, such as a mouth or limb movement, and also when the animal passively observes an identical or similar action performed by another individual. Brain-imaging studies in humans conducted over the last 20 years have repeatedly attempted to reveal analogous brain regions with mirror properties in humans, with broad and often speculative claims about their functional significance across a range of cognitive domains, from language to social cognition. Despite such concerted efforts, the likely neural substrates of these mirror regions have remained controversial, and indeed the very existence of a distinct subcategory of human neurons with mirroring properties has been questioned. Here we used activation likelihood estimation (ALE), to provide a quantitative index of the consistency of patterns of fMRI activity measured in human studies of action observation and action execution. From an initial sample of more than 300 published works, data from 125 papers met our strict inclusion and exclusion criteria. The analysis revealed 14 separate clusters in which activation has been consistently attributed to brain regions with mirror properties, encompassing 9 different Brodmann areas. These clusters were located in areas purported to show mirroring properties in the macaque, such as the inferior parietal lobule, inferior frontal gyrus and the adjacent ventral premotor cortex, but surprisingly also in regions such as the primary visual cortex, cerebellum and parts of the limbic system. Our findings suggest a core network of human brain regions that possess mirror properties associated with action observation and execution, with additional areas recruited during tasks that engage non-motor functions, such as auditory, somatosensory and affective components. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

IgY14 and SuperMix immunoaffinity separations coupled with liquid chromatography-mass spectrometry for human plasma proteomic biomarker discovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Tujin; Zhou, Jianying; Gritsenko, Marina A.

2012-02-01

Interest in the application of advanced proteomics technologies to human blood plasma- or serum-based clinical samples for the purpose of discovering disease biomarkers continues to grow; however, the enormous dynamic range of protein concentrations in these types of samples (often >10 orders of magnitude) represents a significant analytical challenge, particularly for detecting low-abundance candidate biomarkers. In response, immunoaffinity separation methods for depleting multiple high- and moderate-abundance proteins have become key tools for enriching low-abundance proteins and enhancing detection of these proteins in plasma proteomics. Herein, we describe IgY14 and tandem IgY14-Supermix separation methods for removing 14 high-abundance and up tomore » 60 moderate-abundance proteins, respectively, from human blood plasma and highlight their utility when combined with liquid chromatography-tandem mass spectrometry for interrogating the human plasma proteome.« less

Optimization of the first dimension for separation by two-dimensional gel electrophoresis of basic proteins from human brain tissue.

PubMed

Pennington, Kyla; McGregor, Emma; Beasley, Clare L; Everall, Ian; Cotter, David; Dunn, Michael J

2004-01-01

A major cause of poor resolution in the alkaline pH range of two-dimensional electrophoresis (2-DE) gels is unsatisfactory separation of basic proteins in the first dimension. We have compared methods for the separation of basic proteins in the isoelectric focusing dimension of human brain proteins. The combined use of anodic cup-loading and the hydroxyethyldisulphide containing solution (DeStreak) produced better resolution in both analytical and micropreparative protein loaded 2-DE gels than the other methods investigated.

An Approach to Using Toxicogenomic Data in US EPA Human ...

EPA Pesticide Factsheets

This draft report is a description of an approach to evaluate genomic data for use in risk assessment and a case study to illustrate the approach. The dibutyl phthalate (DBP) case study example focuses on male reproductive developmental effects and the qualitative application of the available genomic data. The case study presented in this draft document is a separate activity from any of the ongoing IRIS human health assessments for the phthalates. This draft report is a description of an approach to evaluate genomic data for use in risk assessment and a case study to illustrate the approach. The dibutyl phthalate (DBP) case study example focuses on male reproductive developmental effects and the qualitative application of the available genomic data.

Does the impact of biodiversity differ between emerging and endemic pathogens? The need to separate the concepts of hazard and risk.

PubMed

Hosseini, Parviez R; Mills, James N; Prieur-Richard, Anne-Hélène; Ezenwa, Vanessa O; Bailly, Xavier; Rizzoli, Annapaola; Suzán, Gerardo; Vittecoq, Marion; García-Peña, Gabriel E; Daszak, Peter; Guégan, Jean-François; Roche, Benjamin

2017-06-05

Biodiversity is of critical value to human societies, but recent evidence that biodiversity may mitigate infectious-disease risk has sparked controversy among researchers. The majority of work on this topic has focused on direct assessments of the relationship between biodiversity and endemic-pathogen prevalence, without disentangling intervening mechanisms; thus study outcomes often differ, fuelling more debate. Here, we suggest two critical changes to the approach researchers take to understanding relationships between infectious disease, both endemic and emerging, and biodiversity that may help clarify sources of controversy. First, the distinct concepts of hazards versus risks need to be separated to determine how biodiversity and its drivers may act differently on each. This distinction is particularly important since it illustrates that disease emergence drivers in humans could be quite different to the general relationship between biodiversity and transmission of endemic pathogens. Second, the interactive relationship among biodiversity, anthropogenic change and zoonotic disease risk, including both direct and indirect effects, needs to be recognized and accounted for. By carefully disentangling these interactions between humans' activities and pathogen circulation in wildlife, we suggest that conservation efforts could mitigate disease risks and hazards in novel ways that complement more typical disease control efforts.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'. © 2017 The Author(s).

Induction of a massive endoplasmic reticulum and perinuclear space expansion by expression of lamin B receptor mutants and the related sterol reductases TM7SF2 and DHCR7.

PubMed

Zwerger, Monika; Kolb, Thorsten; Richter, Karsten; Karakesisoglou, Iakowos; Herrmann, Harald

2010-01-15

Lamin B receptor (LBR) is an inner nuclear membrane protein involved in tethering the nuclear lamina and the underlying chromatin to the nuclear envelope. In addition, LBR exhibits sterol reductase activity. Mutations in the LBR gene cause two different human diseases: Pelger-Huët anomaly and Greenberg skeletal dysplasia, a severe chrondrodystrophy causing embryonic death. Our study aimed at investigating the effect of five LBR disease mutants on human cultured cells. Three of the tested LBR mutants caused a massive compaction of chromatin coincidental with the formation of a large nucleus-associated vacuole (NAV) in several human cultured cell lines. Live cell imaging and electron microscopy revealed that this structure was generated by the separation of the inner and outer nuclear membrane. During NAV formation, nuclear pore complexes and components of the linker of nucleoskeleton and cytoskeleton complex were lost in areas of membrane separation. Concomitantly, a large number of smaller vacuoles formed throughout the cytoplasm. Notably, forced expression of the two structurally related sterol reductases transmembrane 7 superfamily member 2 and 7-dehydrocholesterol reductase caused, even in their wild-type form, a comparable phenotype in susceptible cell lines. Hence, LBR mutant variants and sterol reductases can severely interfere with the regular organization of the nuclear envelope and the endoplasmic reticulum.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tu, J.I.; Brennan, J.; Stouffer, B.

Fosinopril (SQ 28,555) is a member of a new chemical class of angiotensin converting enzyme inhibitors being developed by The Squibb Institute for Medical Research. During or following absorption, fosinopril, a prodrug, is hydrolyzed pharmacologically to the active diacid, SQ 27,519. A specific radioimmunoassay (RIA) for the measurement of SQ 27,519 in human serum has been developed. The assay utilizes a specific SQ 27,519 antibody, 125I-iodohistamine-SQ 27,519 radiolabel, and human serum standards. Satisfactory zero binding and assay sensitivity are achieved after a 2-h incubation at room temperature. Separation of the antibody-bound and free radiolabeled antigens is achieved by using polyethylenemore » glycol-goat anti-rabbit gamma globulin separant. Recovery efficiencies ranged from 97.2 to 109.4%. The assay exhibited little or no cross-reactivity with captopril. Cross-reactivities for prodrug (SQ 28,555) and phenolic SQ 27,519 were 5 and 9%, respectively. Intra-assay variability (3.3-5.6%) and interassay variability (7.1-6.6%) were observed. Linear regression analysis indicates that RIA and (14C) thin-layer radiochromatography (TLRC) methods gave a highly significant correlation (RIA = 1.0 (14C)TLRC + 0.17, r = 0.991). Pharmacokinetic profiles of patient sera containing SQ 27,519 obtained by RIA and (14C)TLRC are identical. The RIA has been used routinely in support of the bioavailability and pharmacokinetic studies of fosinopril in humans.« less

Does the impact of biodiversity differ between emerging and endemic pathogens? The need to separate the concepts of hazard and risk

PubMed Central

Hosseini, Parviez R.; Mills, James N.; Prieur-Richard, Anne-Hélène; Bailly, Xavier; Rizzoli, Annapaola; Suzán, Gerardo; Vittecoq, Marion; Daszak, Peter; Guégan, Jean-François

2017-01-01

Biodiversity is of critical value to human societies, but recent evidence that biodiversity may mitigate infectious-disease risk has sparked controversy among researchers. The majority of work on this topic has focused on direct assessments of the relationship between biodiversity and endemic-pathogen prevalence, without disentangling intervening mechanisms; thus study outcomes often differ, fuelling more debate. Here, we suggest two critical changes to the approach researchers take to understanding relationships between infectious disease, both endemic and emerging, and biodiversity that may help clarify sources of controversy. First, the distinct concepts of hazards versus risks need to be separated to determine how biodiversity and its drivers may act differently on each. This distinction is particularly important since it illustrates that disease emergence drivers in humans could be quite different to the general relationship between biodiversity and transmission of endemic pathogens. Second, the interactive relationship among biodiversity, anthropogenic change and zoonotic disease risk, including both direct and indirect effects, needs to be recognized and accounted for. By carefully disentangling these interactions between humans' activities and pathogen circulation in wildlife, we suggest that conservation efforts could mitigate disease risks and hazards in novel ways that complement more typical disease control efforts. This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’. PMID:28438918

Antiproliferative activity of Haematoxylum brasiletto H. Karst

PubMed Central

Bello-Martínez, J; Jiménez-Estrada, M; Rosas-Acevedo, JL; Avila-Caballero, LP; Vidal-Gutierrez, M; Patiño-Morales, C; Ortiz-Sánchez, E; Robles-Zepeda, RE

2017-01-01

Background: Haematoxylum brasiletto is a tree that grows in Central America, commonly known as “Palo de Brasil,” which is used in the traditional medicine for the treatment of cancer and gastric ulcers. Objective: The aim of this study was to isolate the compounds responsible for antiproliferative activity of H. brasiletto. Materials and Methods: A bioassay-guided fractionation of ethanol extract of H. brasiletto was performed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide cell proliferation assay to measure the antiproliferative activity on six human cancer cell lines (A549, LS180, HeLa, SiHa, MDA-MB-231, and NCI-H1299) and one human noncancer cell line (ARPE-19). The ethanol extract was partitioned with hexane, dichloromethane, and ethyl acetate. The active dichloromethane fraction was fractioned by silica-column chromatography, and active subfractions were separated using preparative-thin layer chromatography. The chemical structure of an isolated compound was elucidated with different chemical and spectroscopic methods. Results: The flavonoid brazilin (1) was isolated from the heartwood of H. brasiletto. The measurement of antiproliferative activity showed that brazilin can inhibit the growth of SiHa, MDA-MB-231, A549, and NCI-H1299 cell lines by 50% at doses of 44.3, 48.7, 45.4, and 48.7 μM, respectively. Furthermore, the flavonoid showed a high antiproliferative activity on LS 180 and HeLa with IC50 values of 62.2 and 71.9 μM, respectively. Brazilin also exhibited a high antiproliferative activity on the human noncancer cell line ARPE-19 with an IC50 value of 37.9 μM. Conclusions: Brazilin: (6aS, 11bR)-7,11b-Dihidro-6H-indeno[2,1-c] cromeno-3,6a, 9,10-tetrol was isolated; this compound demonstrated antiproliferative activity against several human cancer cell lines. This work demonstrated that brazilin, a flavonoid isolated and characterized of H. brasiletto, has antiproliferative activity against cancer cell lines. SUMMARY The flavonoid brazilin was isolated from the heartwood of H. brasilettoBrazilin is able to inhibit the growth of SiHa, MDA-MB-231, A549 and NCI- H1299 cancerous cell linesBrazilin exhibited a moderate antiproliferative activity on the human non-cancer cell line ARPE-19Brazilin demonstrated to have antiproliferative activity against human cancer cell lines and could be a potential source of anticancer agents. Abbreviations used: MTT: [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium]; FBS: Fetal bovine serum; TLC: Thin layer chromatography. PMID:28808394

Loss of propiconazole and its four stereoisomers from the water phase of two soil-water slurries as measured by capillary electrophoresis.

PubMed

Garrison, Arthur W; Avants, Jimmy K; Miller, Rebecca D

2011-08-01

Propiconazole is a chiral fungicide used in agriculture for control of many fungal diseases on a variety of crops. This use provides opportunities for pollution of soil and, subsequently, groundwater. The rate of loss of propiconazole from the water phase of two different soil-water slurries spiked with the fungicide at 50 mg/L was followed under aerobic conditions over five months; the t(1/2) was 45 and 51 days for the two soil slurries. To accurately assess environmental and human risk, it is necessary to analyze the separate stereoisomers of chiral pollutants, because it is known that for most such pollutants, both biotransformation and toxicity are likely to be stereoselective. Micellar electrokinetic chromatography (MEKC), the mode of capillary electrophoresis used for analysis of neutral chemicals, was used for analysis of the four propiconazole stereoisomers with time in the water phase of the slurries. MEKC resulted in baseline separation of all stereoisomers, while GC-MS using a chiral column gave only partial separation. The four stereoisomers of propiconazole were lost from the aqueous phase of the slurries at experimentally equivalent rates, i.e., there was very little, if any, stereoselectivity. No loss of propiconazole was observed from the autoclaved controls of either soil, indicating that the loss from active samples was most likely caused by aerobic biotansformation, with a possible contribution by sorption to the non-autoclaved active soils. MEKC is a powerful tool for separation of stereoisomers and can be used to study the fate and transformation kinetics of chiral pesticides in water and soil.

Stem cell derived phenotypic human neuromuscular junction model for dose response evaluation of therapeutics.

PubMed

Santhanam, Navaneetha; Kumanchik, Lee; Guo, Xiufang; Sommerhage, Frank; Cai, Yunqing; Jackson, Max; Martin, Candace; Saad, George; McAleer, Christopher W; Wang, Ying; Lavado, Andrea; Long, Christopher J; Hickman, James J

2018-06-01

There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units. A system was developed in which human myotubes and motoneurons derived from stem cells were cultured in a serum-free medium in a BioMEMS construct. The system is composed of two chambers linked by microtunnels to enable axonal outgrowth to the muscle chamber that allows separate stimulation of each component and physiological NMJ function and MN stimulated tetanus. The muscle's contractions, induced by motoneuron activation or direct electrical stimulation, were monitored by image subtraction video recording for both frequency and amplitude. Bungarotoxin, BOTOX ® and curare dose response curves were generated to demonstrate pharmacological relevance of the phenotypic screening device. This quantifiable functional hNMJ system establishes a platform for generating patient-specific NMJ models by including patient-derived iPSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Simultaneous chromatic and luminance human electroretinogram responses.

PubMed

Parry, Neil R A; Murray, Ian J; Panorgias, Athanasios; McKeefry, Declan J; Lee, Barry B; Kremers, Jan

2012-07-01

The parallel processing of information forms an important organisational principle of the primate visual system. Here we describe experiments which use a novel chromatic–achromatic temporal compound stimulus to simultaneously identify colour and luminance specific signals in the human electroretinogram (ERG). Luminance and chromatic components are separated in the stimulus; the luminance modulation has twice the temporal frequency of the chromatic modulation. ERGs were recorded from four trichromatic and two dichromatic subjects (1 deuteranope and 1 protanope). At isoluminance, the fundamental (first harmonic) response was elicited by the chromatic component in the stimulus. The trichromatic ERGs possessed low-pass temporal tuning characteristics, reflecting the activity of parvocellular post-receptoral mechanisms. There was very little first harmonic response in the dichromats' ERGs. The second harmonic response was elicited by the luminance modulation in the compound stimulus and showed, in all subjects, band-pass temporal tuning characteristic of magnocellular activity. Thus it is possible to concurrently elicit ERG responses from the human retina which reflect processing in both chromatic and luminance pathways. As well as providing a clear demonstration of the parallel nature of chromatic and luminance processing in the human retina, the differences that exist between ERGs from trichromatic and dichromatic subjects point to the existence of interactions between afferent post-receptoral pathways that are in operation from the earliest stages of visual processing.

Urokinase-type plasminogen activator: a new target for male contraception?

PubMed

Qin, Ying; Han, Yan; Xiong, Cheng-Liang; Li, Hong-Gang; Hu, Lian; Zhang, Ling

2015-01-01

Urokinase-type plasminogen activator (uPA) is closely related to male reproduction. With the aim of investigating the possibility for uPA as a potential contraceptive target, in the present work, Kunming male mice were immunized by human uPA subcutaneous injection at three separate doses for 3 times. Then the potency of the anti-human uPA antibody in serum was analyzed, and mouse fertility was evaluated. Serum antibody titers for human uPA in immunized groups all reached 1:10,240 or higher levels by enzyme linked immunosorbent assay, and mating experiments revealed that pregnancy rates and the mean number of embryos implanted after mating declined obviously (P < 0.05) when compared with control groups. However, the mating capacity and reproductive organ weights had no obvious change, and histological analysis of the testes and epididymides also showed normal morphology for immunized male mice. Sperm function tests suggested that the sperm concentration, sperm viability, sperm motility, and in vitro fertilization rate for the cauda epididymis sperm in uPA-immunized groups were lower than those in the controls (P < 0.05). Together, these observations indicated that subcutaneous injection human uPA to the male mice could effectively reduce their fertility, and uPA could become a new target for immunocontraception in male contraceptive development.

Cardiovascular fitness, cortical plasticity, and aging.

PubMed

Colcombe, Stanley J; Kramer, Arthur F; Erickson, Kirk I; Scalf, Paige; McAuley, Edward; Cohen, Neal J; Webb, Andrew; Jerome, Gerry J; Marquez, David X; Elavsky, Steriani

2004-03-02

Cardiovascular fitness is thought to offset declines in cognitive performance, but little is known about the cortical mechanisms that underlie these changes in humans. Research using animal models shows that aerobic training increases cortical capillary supplies, the number of synaptic connections, and the development of new neurons. The end result is a brain that is more efficient, plastic, and adaptive, which translates into better performance in aging animals. Here, in two separate experiments, we demonstrate for the first time to our knowledge, in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task. Specifically, highly fit (Study 1) or aerobically trained (Study 2) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning, when compared with low-fit (Study 1) or nonaerobic control (Study 2) participants. Additionally, in both studies there exist groupwise differences in activation of the anterior cingulate cortex, which is thought to monitor for conflict in the attentional system, and signal the need for adaptation in the attentional network. These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain, and may serve to reduce both biological and cognitive senescence in humans.

Efferent influences on the bioelectrical activity of the retina in primates.

PubMed

Ortiz, Gonzalo; Odom, J Vernon; Passaglia, Christopher L; Tzekov, Radouil T

2017-02-01

The existence of retinopetal (sometimes referred to as "efferent" or "centrifugal") axons in the mammalian optic nerve is a topic of long-standing debate. Opposition is fading as efferent innervation of the retina has now been widely documented in rodents and other animals. The existence and function of an efferent system in humans and non-human primates has not, though, been definitively established. Such a feedback pathway could have important functional, clinical, and experimental significance to the field of vision science and ophthalmology. Following a comprehensive literature review (PubMed and Google Scholar, until July 2016), we present evidence regarding a system that can influence the bioelectrical activity of the retina in primates. Anatomical and physiological evidences are presented separately. Improvements in histological staining and the advent of retrograde nerve fiber tracers have allowed for more confidence in the identification of efferent optic nerve fibers, including back to their point of origin. Even with the accumulation of more modern anatomical and physiological evidence, some limitations and uncertainties about crucial details regarding the origins and role of a top-down, efferent system still exist. However, the summary of the evidence from earlier and more modern studies makes a compelling case in support of such a system in humans and non-human primates.

SEIPS 2.0: a human factors framework for studying and improving the work of healthcare professionals and patients.

PubMed

Holden, Richard J; Carayon, Pascale; Gurses, Ayse P; Hoonakker, Peter; Hundt, Ann Schoofs; Ozok, A Ant; Rivera-Rodriguez, A Joy

2013-01-01

Healthcare practitioners, patient safety leaders, educators and researchers increasingly recognise the value of human factors/ergonomics and make use of the discipline's person-centred models of sociotechnical systems. This paper first reviews one of the most widely used healthcare human factors systems models, the Systems Engineering Initiative for Patient Safety (SEIPS) model, and then introduces an extended model, 'SEIPS 2.0'. SEIPS 2.0 incorporates three novel concepts into the original model: configuration, engagement and adaptation. The concept of configuration highlights the dynamic, hierarchical and interactive properties of sociotechnical systems, making it possible to depict how health-related performance is shaped at 'a moment in time'. Engagement conveys that various individuals and teams can perform health-related activities separately and collaboratively. Engaged individuals often include patients, family caregivers and other non-professionals. Adaptation is introduced as a feedback mechanism that explains how dynamic systems evolve in planned and unplanned ways. Key implications and future directions for human factors research in healthcare are discussed.

Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus.

PubMed

Sieger, Tomáš; Serranová, Tereza; Růžička, Filip; Vostatek, Pavel; Wild, Jiří; Štastná, Daniela; Bonnet, Cecilia; Novák, Daniel; Růžička, Evžen; Urgošík, Dušan; Jech, Robert

2015-03-10

Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson's disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well.

Collaboration and cogenerativity: on bridging the gaps separating theory-practice and cognition-emotion

NASA Astrophysics Data System (ADS)

Stetsenko, Anna

2008-07-01

In this rejoinder, I comment on how going through the activity of participating in this forum and of engaging in dialogue with my commentators makes sense at several levels—most importantly, at the personal and the conceptual—and how these two levels are intricately connected. The link between the personal and conceptual (cognition and emotion)—their de facto unity—is highlighted through a discussion of a theoretical stance that has to do with ineluctable dialogicality of any and all aspects, incarnations, and expressions of human development, being, and learning. The dialogicality of knowing comes to the fore if knowledge is understood as being part and parcel of ongoing real life activities out in the world imbued with ideology, values, and commitments. In this stance, knowing and acting, words and deeds, theory and practice cannot be ever thought of as separate realms; instead they inevitably and necessarily appear as belonging together and as forming inherent aspects (or dimensions) of one and the same process of people collaboratively engaging with and transforming the world.

Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea.

PubMed

Gurley, Bill J; Swain, Ashley; Hubbard, Martha A; Williams, D Keith; Barone, Gary; Hartsfield, Faith; Tong, Yudong; Carrier, Danielle J; Cheboyina, Shreekar; Battu, Sunil K

2008-07-01

Cytochrome P450 2D6 (CYP2D6), an important CYP isoform with regard to drug-drug interactions, accounts for the metabolism of approximately 30% of all medications. To date, few studies have assessed the effects of botanical supplementation on human CYP2D6 activity in vivo. Six botanical extracts were evaluated in three separate studies (two extracts per study), each incorporating 16 healthy volunteers (eight females). Subjects were randomized to receive a standardized botanical extract for 14 days on separate occasions. A 30-day washout period was interposed between each supplementation phase. In study 1, subjects received milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa). In study 2, kava kava (Piper methysticum) and goldenseal (Hydrastis canadensis) extracts were administered, and in study 3 subjects received St. John's wort (Hypericum perforatum) and Echinacea (Echinacea purpurea). The CYP2D6 substrate, debrisoquine (5 mg), was administered before and at the end of supplementation. Pre- and post-supplementation phenotypic trait measurements were determined for CYP2D6 using 8-h debrisoquine urinary recovery ratios (DURR). Comparisons of pre- and post-supplementation DURR revealed significant inhibition (approximately 50%) of CYP2D6 activity for goldenseal, but not for the other extracts. Accordingly, adverse herb-drug interactions may result with concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 substrates.

Using Smartphones to Detect Earthquakes

NASA Astrophysics Data System (ADS)

Kong, Q.; Allen, R. M.

2012-12-01

We are using the accelerometers in smartphones to record earthquakes. In the future, these smartphones may work as a supplement network to the current traditional network for scientific research and real-time applications. Given the potential number of smartphones, and small separation of sensors, this new type of seismic dataset has significant potential provides that the signal can be separated from the noise. We developed an application for android phones to record the acceleration in real time. These records can be saved on the local phone or transmitted back to a server in real time. The accelerometers in the phones were evaluated by comparing performance with a high quality accelerometer while located on controlled shake tables for a variety of tests. The results show that the accelerometer in the smartphone can reproduce the characteristic of the shaking very well, even the phone left freely on the shake table. The nature of these datasets is also quite different from traditional networks due to the fact that smartphones are moving around with their owners. Therefore, we must distinguish earthquake signals from other daily use. In addition to the shake table tests that accumulated earthquake records, we also recorded different human activities such as running, walking, driving etc. An artificial neural network based approach was developed to distinguish these different records. It shows a 99.7% successful rate of distinguishing earthquakes from the other typical human activities in our database. We are now at the stage ready to develop the basic infrastructure for a smartphone seismic network.

Development and Validation of a Micellar Capillary Electrophoresis Method for Determination of IFNβ-1b in Lyophilized Formulation of a Biosimilar Product

PubMed Central

Dadgarnejad, Manuchehr; Rastegar, Hosein; Ilka, Hooshmand; Shekarchi, Maryam; Adib, Nooshin; Alebouyeh, Mahmood; Keypour, Nadia; Shoeibi, Shahram; Kobarfard, Farzad; Fazeli, Mohammad Reza

2015-01-01

Human interferons (IFNs) are key cytokines secreted by immune system. They have several effects such as antiviral and anti tumors activity, activating immune cells and healing of multiple sclerosis. The type IFNs present in humans are α ,β and Υ. IFN β is a polypeptide, normally produced by fibroblasts and seems to be more species-specific than IFN. Structural properties of IFNs are important for their biologic effects. There are a few analytical techniques for separation, identification and determination of IFNs in its formulations such as mass spectroscopy, RP-HPLC and capillary electrophoresis (CE). In this study we used Micellar Electrokinetic Chromatography (MEKC) as a unique mode of CE because of its capability to separate neutral as well as charged solutes. We used sodium tetraborate (Borax) as buffer without any modifier and sodium dodecyl sulfate (SDS) as surfactant. The optimum MECK running buffer consisted of Borate 50 Mm; SDS 20 mM pH =9.6. The validated method was used for determination of the IFN β-1b formulation which is manufactured in Iran. From 9 collected different batches, all of them had acceptable potency as claimed on their label with average 102.25 ±10.030 %. This is the first time that a MEKC method is introduced for quantification of IFN β-1b in its pharmaceutical dosage forms. The method is reliable safe, rapid and accurate. PMID:26330863

Development and Validation of a Micellar Capillary Electrophoresis Method for Determination of IFNβ-1b in Lyophilized Formulation of a Biosimilar Product.

PubMed

Dadgarnejad, Manuchehr; Rastegar, Hosein; Ilka, Hooshmand; Shekarchi, Maryam; Adib, Nooshin; Alebouyeh, Mahmood; Keypour, Nadia; Shoeibi, Shahram; Kobarfard, Farzad; Fazeli, Mohammad Reza

2015-01-01

Human interferons (IFNs) are key cytokines secreted by immune system. They have several effects such as antiviral and anti tumors activity, activating immune cells and healing of multiple sclerosis. The type IFNs present in humans are α ,β and Υ. IFN β is a polypeptide, normally produced by fibroblasts and seems to be more species-specific than IFN. Structural properties of IFNs are important for their biologic effects. There are a few analytical techniques for separation, identification and determination of IFNs in its formulations such as mass spectroscopy, RP-HPLC and capillary electrophoresis (CE). In this study we used Micellar Electrokinetic Chromatography (MEKC) as a unique mode of CE because of its capability to separate neutral as well as charged solutes. We used sodium tetraborate (Borax) as buffer without any modifier and sodium dodecyl sulfate (SDS) as surfactant. The optimum MECK running buffer consisted of Borate 50 Mm; SDS 20 mM pH =9.6. The validated method was used for determination of the IFN β-1b formulation which is manufactured in Iran. From 9 collected different batches, all of them had acceptable potency as claimed on their label with average 102.25 ±10.030 %. This is the first time that a MEKC method is introduced for quantification of IFN β-1b in its pharmaceutical dosage forms. The method is reliable safe, rapid and accurate.

Visualization of light propagation in visible Chinese human head for functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Li, Ting; Gong, Hui; Luo, Qingming

2011-04-01

Using the visible Chinese human data set, which faithfully represents human anatomy, we visualize the light propagation in the head in detail based on Monte Carlo simulation. The simulation is verified to agree with published experimental results in terms of a differential path-length factor. The spatial sensitivity profile turns out to seem like a fat tropical fish with strong distortion along the folding cerebral surface. The sensitive brain region covers the gray matter and extends to the superficial white matter, leading to a large penetration depth (>3 cm). Finally, the optimal source-detector separation is suggested to be narrowed down to 3-3.5 cm, while the sensitivity of the detected signal to brain activation reaches the peak of 8%. These results indicate that the cerebral cortex folding geometry actually has substantial effects on light propagation, which should be necessarily considered for applications of functional near-infrared spectroscopy.

ANABOLIC-ANDROGENIC STEROID DEPENDENCE? INSIGHTS FROM ANIMALS AND HUMANS

PubMed Central

Wood, Ruth I.

2008-01-01

Anabolic-androgenic steroids (AAS) are drugs of abuse. They are taken in large quantities by athletes and others to increase performance, with negative health consequences. As a result, in 1991 testosterone and related AAS were declared controlled substances. However, the relative abuse and dependence liability of AAS have not been fully characterized. In humans, it is difficult to separate the direct psychoactive effects of AAS from reinforcement due to their systemic anabolic effects. However, using conditioned place preference and self-administration, studies in animals have demonstrated that AAS are reinforcing in a context where athletic performance is irrelevant. Furthermore, AAS share brain sites of action and neurotransmitter systems in common with other drugs of abuse. In particular, recent evidence links AAS with opioids. In humans, AAS abuse is associated with prescription opioid use. In animals, AAS overdose produces symptoms resembling opioid overdose, and AAS modify the activity of the endogenous opioid system. PMID:18275992

The cerebral signature for pain perception and its modulation.

PubMed

Tracey, Irene; Mantyh, Patrick W

2007-08-02

Our understanding of the neural correlates of pain perception in humans has increased significantly since the advent of neuroimaging. Relating neural activity changes to the varied pain experiences has led to an increased awareness of how factors (e.g., cognition, emotion, context, injury) can separately influence pain perception. Tying this body of knowledge in humans to work in animal models of pain provides an opportunity to determine common features that reliably contribute to pain perception and its modulation. One key system that underpins the ability to change pain intensity is the brainstem's descending modulatory network with its pro- and antinociceptive components. We discuss not only the latest data describing the cerebral signature of pain and its modulation in humans, but also suggest that the brainstem plays a pivotal role in gating the degree of nociceptive transmission so that the resultant pain experienced is appropriate for the particular situation of the individual.

Tuning of Human Modulation Filters Is Carrier-Frequency Dependent

PubMed Central

Simpson, Andrew J. R.; Reiss, Joshua D.; McAlpine, David

2013-01-01

Recent studies employing speech stimuli to investigate ‘cocktail-party’ listening have focused on entrainment of cortical activity to modulations at syllabic (5 Hz) and phonemic (20 Hz) rates. The data suggest that cortical modulation filters (CMFs) are dependent on the sound-frequency channel in which modulations are conveyed, potentially underpinning a strategy for separating speech from background noise. Here, we characterize modulation filters in human listeners using a novel behavioral method. Within an ‘inverted’ adaptive forced-choice increment detection task, listening level was varied whilst contrast was held constant for ramped increments with effective modulation rates between 0.5 and 33 Hz. Our data suggest that modulation filters are tonotopically organized (i.e., vary along the primary, frequency-organized, dimension). This suggests that the human auditory system is optimized to track rapid (phonemic) modulations at high sound-frequencies and slow (prosodic/syllabic) modulations at low frequencies. PMID:24009759

The effects of 7.5% NaCl/6% dextran 70 on coagulation and platelet aggregation in humans

NASA Technical Reports Server (NTRS)

Hess, J. R.; Dubick, M. A.; Summary, J. J.; Bangal, N. R.; Wade, C. E.

1992-01-01

The combination solution of 7.5% NaCl/6% dextran 70 (HSD) administered IV gives hemodynamic improvement in the treatment of hemorrhagic hypotension. Since earlier dextran solutions were reported to interfere with blood coagulation, the effects of HSD on the prothrombin time (PT), the activated partial thromboplastin time (APTT), platelet aggregation, and platelet concentration were studied. The HSD mixed with human plasma (1:5 and 1:10) slightly prolonged PT, but had no effect on the APTT, compared with saline controls. The HSD also decreased human platelet aggregation at the 1:5 dilution. In separate mixing studies, the hypertonic saline component of HSD was associated with the prolongation of PT and decreased platelet aggregation. The data from these studies indicate that at its proposed therapeutic dose, HSD is expected to have minimal effect on blood coagulation.

Midcingulate Motor Map and Feedback Detection: Converging Data from Humans and Monkeys

PubMed Central

Procyk, Emmanuel; Wilson, Charles R. E.; Stoll, Frederic M.; Faraut, Maïlys C. M.; Petrides, Michael; Amiez, Céline

2016-01-01

The functional and anatomical organization of the cingulate cortex across primate species is the subject of considerable and often confusing debate. The functions attributed to the midcingulate cortex (MCC) embrace, among others, feedback processing, pain, salience, action-reward association, premotor functions, and conflict monitoring. This multiplicity of functional concepts suggests either unresolved separation of functional contributions or integration and convergence. We here provide evidence from recent experiments in humans and from a meta-analysis of monkey data that MCC feedback-related activity is generated in the rostral cingulate premotor area by specific body maps directly related to the modality of feedback. As such, we argue for an embodied mechanism for adaptation and exploration in MCC. We propose arguments and precise tools to resolve the origins of performance monitoring signals in the medial frontal cortex, and to progress on issues regarding homology between human and nonhuman primate cingulate cortex. PMID:25217467

Identification of ALK as the Major Familial Neuroblastoma Predisposition Gene

PubMed Central

Mossë, Yalë P; Laudenslager, Marci; Longo, Luca; Cole, Kristina A; Wood, Andrew; Attiyeh, Edward F; Laquaglia, Michael J; Sennett, Rachel; Lynch, Jill E; Perri, Patrizia; Laureys, Geneviève; Speleman, Frank; Hakonarson, Hakon; Torkamani, Ali; Schork, Nicholas J; Brodeur, Garrett M; Tonini, Gian Paolo; Rappaport, Eric; Devoto, Marcella; Maris, John M

2009-01-01

SUMMARY Survival rates for the childhood cancer neuroblastoma have not substantively improved despite dramatic escalation in chemotherapy intensity. Like most human cancers, this embryonal malignancy can be inherited, but the genetic etiology of familial and sporadically occurring neuroblastoma was largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase gene (ALK) explain the majority of hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at the short arm of chromosome 2 (maximum nonparametric LOD=4.23 at rs1344063) using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate missense mutations in the tyrosine kinase domain of ALK (G1128A, R1192P and R1275Q) that segregated with the disease in eight separate families. Examination of 491 sporadically occurring human neuroblastoma samples showed that the ALK locus was gained in 22.8%, and highly amplified in an additional 3.3%, and that these aberrations were highly associated with death from disease (P=0.0003). Resequencing of 194 high-risk neuroblastoma samples showed somatically acquired mutations within the tyrosine kinase domain in 12.4%. Nine of the ten mutations map to critical regions of the kinase domain and were predicted to be oncogenic drivers with high probability. Mutations resulted in constitutive phosphorylation consistent with activation, and targeted knockdown of ALK mRNA resulted in profound growth inhibition of 4 of 4 cell lines harboring mutant or amplified ALK, as well as 2 of 6 wild type for ALK. Our results demonstrate that heritable mutations of ALK are the major cause of familial neuroblastoma, and that germline or acquired activation of this cell surface kinase is a tractable therapeutic target for this lethal pediatric malignancy. PMID:18724359

The anti-tumour activity of rLj-RGD4, an RGD toxin protein from Lampetra japonica, on human laryngeal squamous carcinoma Hep-2 cells in nude mice.

PubMed

Shao, Fangyu; Lv, Mei; Zheng, Yuanyuan; Jiang, Junshu; Wang, Yue; Lv, Li; Wang, Jihong

2015-12-01

The objective of this study is to investigate the antiproliferative activity and mechanism of integrin-binding rLj-RGD4 in a Hep-2 human laryngeal carcinoma-bearing nude mouse model. Human laryngeal squamous carcinoma cells (Hep-2) were inoculated subcutaneously into the axilla of nude mice to generate a Hep-2 human laryngeal carcinoma-bearing nude mouse model. When the Hep-2 xenograft model was successfully established, the animals were randomly separated into five groups. Three groups were treated with different dosages of rLj-RGD4. Cisplatin was administered to the positive control group, and normal saline (NaCl) was administered to the negative control group for 3 weeks. The body weights and the survival of the nude mice were evaluated, and the volumes and weights of the solid tumours were measured. The mechanism underlying rLj-RGD4 inhibition of tumour growth in transplanted Hep-2 human laryngeal carcinoma-bearing nude mice was evaluated by haematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL), measurement of intratumoural microvessel density (MVD), Western blotting, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The tumour volumes and weights of the treatment groups were reduced compared with the model group, and survival times were improved by rLj-RGD4 treatment in Hep-2 human laryngeal carcinoma-bearing nude mice. The number of apoptotic Hep-2 human cells and intratumoural MVD significantly decreased after the administration of rLj-RGD4. In the xenograft tissue of animals treated with rLj-RGD4, FAK, PI3K, and Akt expression was unaltered, whereas P-FAK, P-PI3K, Bcl-2, P-Akt, and VEGF levels were down-regulated. In addition, activated caspase-3, activated caspase-9, and Bax levels were up-regulated. rLj-RGD4 exhibits potent in vivo activity and inhibits the growth of transplanted Hep-2 human laryngeal carcinoma cells in a nude mouse model. Thus, these results indicate that the recombinant RGD toxin protein rLj-RGD4 may serve as a potent clinical therapy for human laryngeal squamous carcinoma. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

An fMRI study of the brain responses of traumatized mothers to viewing their toddlers during separation and play.

PubMed

Schechter, Daniel S; Moser, Dominik A; Wang, Zhishun; Marsh, Rachel; Hao, XueJun; Duan, Yunsuo; Yu, Shan; Gunter, Benjamin; Murphy, David; McCaw, Jaime; Kangarlu, Alayar; Willheim, Erica; Myers, Michael M; Hofer, Myron A; Peterson, Bradley S

2012-11-01

This study tested whether mothers with interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) vs healthy controls (HC) would show greater limbic and less frontocortical activity when viewing young children during separation compared to quiet play. Mothers of 20 children (12-42 months) participated: 11 IPV-PTSD mothers and 9 HC with no PTSD. During fMRI, mothers watched epochs of play and separation from their own and unfamiliar children. The study focused on comparison of PTSD mothers vs HC viewing children in separation vs play, and viewing own vs unfamiliar children in separation. Both groups showed distinct patterns of brain activation in response to viewing children in separation vs play. PTSD mothers showed greater limbic and less frontocortical activity (BA10) than HC. PTSD mothers also reported feeling more stressed than HC when watching own and unfamiliar children during separation. Their self-reported stress was associated with greater limbic and less frontocortical activity. Both groups also showed distinct patterns of brain activation in response to viewing their own vs unfamiliar children during separation. PTSD mothers' may not have access to frontocortical regulation of limbic response upon seeing own and unfamiliar children in separation. This converges with previously reported associations of maternal IPV-PTSD and atypical caregiving behavior following separation.

The role of early visual cortex in visual short-term memory and visual attention.

PubMed

Offen, Shani; Schluppeck, Denis; Heeger, David J

2009-06-01

We measured cortical activity with functional magnetic resonance imaging to probe the involvement of early visual cortex in visual short-term memory and visual attention. In four experimental tasks, human subjects viewed two visual stimuli separated by a variable delay period. The tasks placed differential demands on short-term memory and attention, but the stimuli were visually identical until after the delay period. Early visual cortex exhibited sustained responses throughout the delay when subjects performed attention-demanding tasks, but delay-period activity was not distinguishable from zero when subjects performed a task that required short-term memory. This dissociation reveals different computational mechanisms underlying the two processes.

Interconnection between thyroid hormone signalling pathways and parvovirus cytotoxic functions.

PubMed Central

Vanacker, J M; Laudet, V; Adelmant, G; Stéhelin, D; Rommelaere, J

1993-01-01

Nonstructural (NS) proteins of autonomous parvoviruses can repress expression driven by heterologous promoters, an activity which thus far has not been separated from their cytotoxic effects. It is shown here that, in transient transfection assays, the NS-1 protein of the parvovirus minute virus of mice (MVMp) activates the promoter of the human c-erbA1 gene, encoding the thyroid hormone (T3) receptor alpha. The endogenous c-erbA1 promoter is also a target for induction upon MVMp infection. Moreover, T3 was found to up-modulate the level of cell sensitivity to parvovirus attack. These data suggest an interconnection between T3 signalling and NS cytotoxic pathways. Images PMID:8230488

Selenium-containing allophycocyanin purified from selenium-enriched Spirulina platensis attenuates AAPH-induced oxidative stress in human erythrocytes through inhibition of ROS generation.

PubMed

Zhang, Haobin; Chen, Tianfeng; Jiang, Jie; Wong, Yum-Shing; Yang, Fang; Zheng, Wenjie

2011-08-24

Both selenium and allophycocyanin (APC) have been reported to show novel antioxidant activities. In this study, a fast protein liquid chromatographic method for purification of selenium-containing allophycocyanin (Se-APC) from selenium-enriched Spirulina platensis and the protective effect of Se-APC on 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress have been described. After fractionation by ammonium sulfate precipitation, and separation by DEAE-Sepharose ion-exchange and Sephacryl S-300 size exclusion chromatography, Se-APC with purity ratio (A652/A280) of 5.30 and Se concentration of 343.02 μg g(-1) protein was obtained. Se-APC exhibited stronger antioxidant activity than APC by scavenging ABTS (2,2'-azinobis-3-ethylbenzothiazolin-6-sulfonic acid) and AAPH free radicals. The oxidative hemolysis and morphological changes induced by AAPH in human erythrocytes were effectively reversed by coincubation with Se-APC. Lipid oxidation induced by the pro-oxidant agent cupric chloride in human plasma, as evaluated by formation of conjugated diene, was blocked by Se-APC. The accumulation of malondialdehyde, loss of reduced glutathione, and increase in enzyme activities of glutathione peroxidase and reductase induced by AAPH in human erythrocytes were effectively suppressed by Se-APC. Furthermore, Se-APC significantly prevented AAPH-induced intracellular reactive oxygen species (ROS) generation. Taken together, our results suggest that Se-APC demonstrates application potential in treatment of diseases in which excess production of ROS acts as a casual or contributory factor.

Modulating the Activity of the DLPFC and OFC Has Distinct Effects on Risk and Ambiguity Decision-Making: A tDCS Study

PubMed Central

Yang, Xiaolan; Gao, Mei; Shi, Jinchuan; Ye, Hang; Chen, Shu

2017-01-01

Human beings are constantly exposed to two types of uncertainty situations, risk and ambiguity. Neuroscientific studies suggest that the dorsolateral prefrontal cortex (DLPFC) and the orbital frontal cortex (OFC) play significant roles in human decision making under uncertainty. We applied the transcranial direct current stimulation (tDCS) device to modulate the activity of participants’ DLPFC and OFC separately, comparing the causal relationships between people’s behaviors and the activity of the corresponding brain cortex when confronted with situations of risk and ambiguity. Our experiment employed a pre–post design and a risk/ambiguity decision-making task, from which we could calculate the preferences via an estimation model. We found evidences that modulating the activity of the DLPFC using right anodal/left cathodal tDCS significantly enhanced the participants’ preferences for risk, whereas modulating the activity of the OFC with right anodal/left cathodal tDCS significantly decreased the participants’ preferences for ambiguity. The reverse effects were also observed in the reversed tDCS treatments on the two areas. Our results suggest that decision-making processes under risk and ambiguity are complicated and may be encoded in two distinct circuits in our brains as the DLPFC primarily impacts decisions under risk whereas the OFC affects ambiguity. PMID:28878714

Modulating the Activity of the DLPFC and OFC Has Distinct Effects on Risk and Ambiguity Decision-Making: A tDCS Study.

PubMed

Yang, Xiaolan; Gao, Mei; Shi, Jinchuan; Ye, Hang; Chen, Shu

2017-01-01

Human beings are constantly exposed to two types of uncertainty situations, risk and ambiguity. Neuroscientific studies suggest that the dorsolateral prefrontal cortex (DLPFC) and the orbital frontal cortex (OFC) play significant roles in human decision making under uncertainty. We applied the transcranial direct current stimulation (tDCS) device to modulate the activity of participants' DLPFC and OFC separately, comparing the causal relationships between people's behaviors and the activity of the corresponding brain cortex when confronted with situations of risk and ambiguity. Our experiment employed a pre-post design and a risk/ambiguity decision-making task, from which we could calculate the preferences via an estimation model. We found evidences that modulating the activity of the DLPFC using right anodal/left cathodal tDCS significantly enhanced the participants' preferences for risk, whereas modulating the activity of the OFC with right anodal/left cathodal tDCS significantly decreased the participants' preferences for ambiguity. The reverse effects were also observed in the reversed tDCS treatments on the two areas. Our results suggest that decision-making processes under risk and ambiguity are complicated and may be encoded in two distinct circuits in our brains as the DLPFC primarily impacts decisions under risk whereas the OFC affects ambiguity.

Nitrogen inputs accelerate phosphorus cycling rates across a wide variety of terrestrial ecosystems.

PubMed

Marklein, Alison R; Houlton, Benjamin Z

2012-02-01

• Biologically essential elements--especially nitrogen (N) and phosphorus (P)--constrain plant growth and microbial functioning; however, human activities are drastically altering the magnitude and pattern of such nutrient limitations on land. Here we examine interactions between N and P cycles of P mineralizing enzyme activities (phosphatase enzymes) across a wide variety of terrestrial biomes. • We synthesized results from 34 separate studies and used meta-analysis to evaluate phosphatase activity with N, P, or N×P fertilization. • Our results show that N fertilization enhances phosphatase activity, from the tropics to the extra-tropics, both on plant roots and in bulk soils. By contrast, P fertilization strongly suppresses rates of phosphatase activity. • These results imply that phosphatase enzymes are strongly responsive to changes in local nutrient cycle conditions. We also show that plant phosphatases respond more strongly to fertilization than soil phosphatases. The tight coupling between N and P provides a mechanism for recent observations of N and P co-limitation on land. Moreover, our results suggest that terrestrial plants and microbes can allocate excess N to phosphatase enzymes, thus delaying the onset of single P limitation to plant productivity as can occur via human modifications to the global N cycle. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

The Case for the Humanities.

ERIC Educational Resources Information Center

Cary, Michael S.

1981-01-01

Describes the current impoverishment of the humanities and the gulf separating the humanities from the sciences. Discusses the need for adequate humanities instruction at the elementary-secondary level. Suggests that humanities teachers rediscover the Italian Renaissance spirit to improve their teaching. (SB)

Separate neural representations of prediction error valence and surprise: Evidence from an fMRI meta-analysis.

PubMed

Fouragnan, Elsa; Retzler, Chris; Philiastides, Marios G

2018-03-25

Learning occurs when an outcome differs from expectations, generating a reward prediction error signal (RPE). The RPE signal has been hypothesized to simultaneously embody the valence of an outcome (better or worse than expected) and its surprise (how far from expectations). Nonetheless, growing evidence suggests that separate representations of the two RPE components exist in the human brain. Meta-analyses provide an opportunity to test this hypothesis and directly probe the extent to which the valence and surprise of the error signal are encoded in separate or overlapping networks. We carried out several meta-analyses on a large set of fMRI studies investigating the neural basis of RPE, locked at decision outcome. We identified two valence learning systems by pooling studies searching for differential neural activity in response to categorical positive-versus-negative outcomes. The first valence network (negative > positive) involved areas regulating alertness and switching behaviours such as the midcingulate cortex, the thalamus and the dorsolateral prefrontal cortex whereas the second valence network (positive > negative) encompassed regions of the human reward circuitry such as the ventral striatum and the ventromedial prefrontal cortex. We also found evidence of a largely distinct surprise-encoding network including the anterior cingulate cortex, anterior insula and dorsal striatum. Together with recent animal and electrophysiological evidence this meta-analysis points to a sequential and distributed encoding of different components of the RPE signal, with potentially distinct functional roles. © 2018 Wiley Periodicals, Inc.

Diastereomer-specific quantification of bioactive hexosylceramides from bacteria and mammals.

PubMed

von Gerichten, Johanna; Schlosser, Kerstin; Lamprecht, Dominic; Morace, Ivan; Eckhardt, Matthias; Wachten, Dagmar; Jennemann, Richard; Gröne, Hermann-Josef; Mack, Matthias; Sandhoff, Roger

2017-06-01

Mammals synthesize, cell-type specifically, the diastereomeric hexosylceramides, β-galactosylceramide (GalCer) and β-glucosylceramide (GlcCer), which are involved in several diseases, such as sphingolipidosis, diabetes, chronic kidney diseases, or cancer. In contrast, Bacteroides fragilis , a member of the human gut microbiome, and the marine sponge, Agelas mauritianus , produce α-GalCer, one of the most potent stimulators for invariant natural killer T cells. To dissect the contribution of these individual stereoisomers to pathologies, we established a novel hydrophilic interaction chromatography-based LC-MS 2 method and separated ( R > 1.5) corresponding diastereomers from each other, independent of their lipid anchors. Testing various bacterial and mammalian samples, we could separate, identify (including the lipid anchor composition), and quantify endogenous β-GlcCer, β-GalCer, and α-GalCer isomers without additional derivatization steps. Thereby, we show a selective decrease of β-GlcCers versus β-GalCers in cell-specific models of GlcCer synthase-deficiency and an increase of specific β-GlcCers due to loss of β-glucoceramidase 2 activity. Vice versa, β-GalCer increased specifically when cerebroside sulfotransferase ( Gal3st1 ) was deleted. We further confirm β-GalCer as substrate of globotriaosylceramide synthase for galabiaosylceramide synthesis and identify additional members of the human gut microbiome to contain immunogenic α-GalCers. Finally, this method is shown to separate corresponding hexosylsphingosine standards, promoting its applicability in further investigations. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Antimicrobial peptide from mucus of Andrias davidianus: screening and purification by magnetic cell membrane separation technique.

PubMed

Pei, Jinjin; Jiang, Lei

2017-07-01

Andrias davidianus, the Chinese giant salamander, has been used in traditional Chinese medicine for many decades. However, no antimicrobial peptides (AMPs) have been described from A. davidianus until now. Here we describe a novel AMP (andricin 01) isolated from the mucus of A. davidianus. The peptide was recovered using an innovative magnetic cell membrane separation technique and was characterised using mass spectrometry and circular dichroism (CD) spectroscopy. Andricin 01 is comprised of ten amino acid residues with a total molecular mass of 955.1 Da. CD spectrum analysis gave results similar to the archetypal random coil spectrum, consistent with the three-dimensional rendering calculated by current bioinformatics tools. Andricin 01 was found to be inhibitory both to Gram-negative and Gram-positive bacteria. Furthermore, the peptide at the minimal bacterial concentration did not show cell cytotoxicity against human hepatocytes or renal cells and did not show haemolytic activity against red blood cells, indicating that is potentially safe and effective for human use. Andricin 01 shows promise as a novel antibacterial that may provide an insight into the development of new drugs. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Pilot and Controller Workload and Situation Awareness with Three Traffic Management Concept

NASA Technical Reports Server (NTRS)

Vu, Kim-Phuong L.; Strybel, Thomas Z.; Kraut, Joshua; Bacon, Paige; Minakata, Katsumi; Battiste, Vernol; Johnson, Walter

2010-01-01

This paper reports on workload and situation awareness of pilots and controllers participating in a human-in-the-loop simulation using three different distributed air-ground traffic management concepts. Eight experimental pilots started the scenario in an en-route phase of flight and were asked to avoid convective weather while performing spacing and merging tasks along with a continuous descent approach (CDA) into Louisville Standiford Airport (SDF). Two controllers managed the sectors through which the pilots flew, with one managing a sector that included the Top of Descent, and the other managing a sector that included the merge point for arrival into SDF. At 3-minute intervals in the scenario, pilots and controllers were probed on their workload or situation awareness. We employed one of three concepts of operation that distributed separation responsibility across human controllers, pilots, and automation to measure changes in operator situation awareness and workload. We found that when pilots were responsible for separation, they had higher levels of awareness, but not necessarily higher levels of workload. When controllers are responsible and actively engaged, they showed higher workload levels compared to pilots and changes in awareness that were dependent on sector characteristics.

Improvement of a patient's circadian rhythm sleep disorders by aripiprazole was associated with stabilization of his bipolar illness.

PubMed

Tashiro, Tetsuo

2017-04-01

Splitting of the behavioural activity phase has been found in nocturnal rodents with suprachiasmatic nucleus (SCN) coupling disorder. A similar phenomenon was observed in the sleep phase in the diurnal human discussed here, suggesting that there are so-called evening and morning oscillators in the SCN of humans. The present case suffered from bipolar disorder refractory to various treatments, and various circadian rhythm sleep disorders, such as delayed sleep phase, polyphasic sleep, separation of the sleep bout resembling splitting and circabidian rhythm (48 h), were found during prolonged depressive episodes with hypersomnia. Separation of sleep into evening and morning components and delayed sleep-offset (24.69-h cycle) developed when lowering and stopping the dose of aripiprazole (APZ). However, resumption of APZ improved these symptoms in 2 weeks, accompanied by improvement in the patient's depressive state. Administration of APZ may improve various circadian rhythm sleep disorders, as well as improve and prevent manic-depressive episodes, via augmentation of coupling in the SCN network. © 2017 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

A coordination polymer based magnetic adsorbent material for hemoglobin isolation from human whole blood, highly selective and recoverable

NASA Astrophysics Data System (ADS)

Zhang, Xiaoxing; Tan, Jipeng; Xu, Xinxin; Shi, Fanian; Li, Guanglu; Yang, Yiqiao

2017-09-01

A composite material has been obtained successfully through the loading of nanoscale coordination polymer on magnetic Fe3O4@SiO2 core-shell particle. In this composite material, coordination polymer nanoparticles distribute uniformly on Fe3O4@SiO2 and these two components are "tied" together firmly with chemical bonds. Adsorption experiments suggest this composite material exhibits very excellent selectivity to hemoglobin. But under the same condition, its adsorption to bovine serum albumin can almost be ignored. This selectivity can be attributed to the existence of hydrophobic interactions between coordination polymer nanoparticle and hemoglobin. For composite material, the hemoglobin adsorption process follows Langmuir model perfectly with high speed. The adsorbed hemoglobin can be eluted easily by sodium dodecyl sulfate stripping reagent with structure and biological activity of hemoglobin keeps well. The composite material was also employed to separate hemoglobin from human whole blood, which receives a very satisfactory result. Furthermore, magnetic measurement reveals ferromagnetic character of this composite material with magnetization saturation 3.56 emu g-1 and this guarantees its excellent magnetic separation performance from the treated solution.

Separation of trait and state in stuttering.

PubMed

Connally, Emily L; Ward, David; Pliatsikas, Christos; Finnegan, Sarah; Jenkinson, Mark; Boyles, Rowan; Watkins, Kate E

2018-04-06

Stuttering is a disorder in which the smooth flow of speech is interrupted. People who stutter show structural and functional abnormalities in the speech and motor system. It is unclear whether functional differences reflect general traits of the disorder or are specifically related to the dysfluent speech state. We used a hierarchical approach to separate state and trait effects within stuttering. We collected sparse-sampled functional MRI during two overt speech tasks (sentence reading and picture description) in 17 people who stutter and 16 fluent controls. Separate analyses identified indicators of: (1) general traits of people who stutter; (2) frequency of dysfluent speech states in subgroups of people who stutter; and (3) the differences between fluent and dysfluent states in people who stutter. We found that reduced activation of left auditory cortex, inferior frontal cortex bilaterally, and medial cerebellum were general traits that distinguished fluent speech in people who stutter from that of controls. The stuttering subgroup with higher frequency of dysfluent states during scanning (n = 9) had reduced activation in the right subcortical grey matter, left temporo-occipital cortex, the cingulate cortex, and medial parieto-occipital cortex relative to the subgroup who were more fluent (n = 8). Finally, during dysfluent states relative to fluent ones, there was greater activation of inferior frontal and premotor cortex extending into the frontal operculum, bilaterally. The above differences were seen across both tasks. Subcortical state effects differed according to the task. Overall, our data emphasise the independence of trait and state effects in stuttering. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Metal-dependent hydrolysis of myelin basic protein by IgGs from the sera of patients with multiple sclerosis.

PubMed

Polosukhina, Dar'ya I; Kanyshkova, Tat'yana G; Doronin, Boris M; Tyshkevich, Olga B; Buneva, Valentina N; Boiko, Alexey N; Gusev, Evgenii I; Nevinsky, Georgy A; Favorova, Olga O

2006-02-28

Homogeneous IgG fractions were obtained by chromatography of the sera of patients with multiple sclerosis (MS) on Protein G-Sepharose under conditions that remove non-specifically bound proteins. These IgGs contained several chelated metals, the relative amount of which decreases in the order: Fe>or=Ca>Cu>or=Zn>or=Mg>or=Mn>or=Pb>or=Co>or=Ni. In contrast to homogeneous IgGs of healthy individuals, Abs of MS patients effectively hydrolyzed human myelin basic protein (MBP). A minor metal-dependent fraction was obtained by chromatography of highly purified IgGs from MS patient on Chelex-100. This IgG fraction did not hydrolyze human MBP in the absence of Me(2+) ions but was activated after addition of Me(2+) ions: Mg(2+)>Mn(2+)>Cu(2+)>Ca(2+). Proteolytic activities of IgGs from other MS patients were also activated by other metal ions (Ni(2+), Fe(2+), Co(2+), Zn(2+), Pb(2+), and Co(2+)) and especially Ni(2+). Ni(2+)-activated IgGs were separated into distinct MBP-hydrolyzing fractions by chromatography on HiTraptrade mark Chelating Sepharose charged with Ni(2+). Detection of Mg(2+)-dependent proteolytic activity in the SDS-PAGE area corresponding only to IgG provided direct evidence that IgG from sera of MS patients possesses metal-dependent human MBP-hydrolyzing activity. Observed properties of MS abzymes distinguish them from other known mammalian metalloproteases and demonstrate their pronounced catalytic diversity. Metal-dependent IgGs from MS patients represent the first example of abzymes with metal-dependent proteolytic activity.

Neural Activity Patterns in the Human Brain Reflect Tactile Stickiness Perception.

PubMed

Kim, Junsuk; Yeon, Jiwon; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

2017-01-01

Our previous human fMRI study found brain activations correlated with tactile stickiness perception using the uni-variate general linear model (GLM) (Yeon et al., 2017). Here, we conducted an in-depth investigation on neural correlates of sticky sensations by employing a multivoxel pattern analysis (MVPA) on the same dataset. In particular, we statistically compared multi-variate neural activities in response to the three groups of sticky stimuli: A supra-threshold group including a set of sticky stimuli that evoked vivid sticky perception; an infra-threshold group including another set of sticky stimuli that barely evoked sticky perception; and a sham group including acrylic stimuli with no physically sticky property. Searchlight MVPAs were performed to search for local activity patterns carrying neural information of stickiness perception. Similar to the uni-variate GLM results, significant multi-variate neural activity patterns were identified in postcentral gyrus, subcortical (basal ganglia and thalamus), and insula areas (insula and adjacent areas). Moreover, MVPAs revealed that activity patterns in posterior parietal cortex discriminated the perceptual intensities of stickiness, which was not present in the uni-variate analysis. Next, we applied a principal component analysis (PCA) to the voxel response patterns within identified clusters so as to find low-dimensional neural representations of stickiness intensities. Follow-up clustering analyses clearly showed separate neural grouping configurations between the Supra- and Infra-threshold groups. Interestingly, this neural categorization was in line with the perceptual grouping pattern obtained from the psychophysical data. Our findings thus suggest that different stickiness intensities would elicit distinct neural activity patterns in the human brain and may provide a neural basis for the perception and categorization of tactile stickiness.

Neural Activity Patterns in the Human Brain Reflect Tactile Stickiness Perception

PubMed Central

Kim, Junsuk; Yeon, Jiwon; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

2017-01-01

Our previous human fMRI study found brain activations correlated with tactile stickiness perception using the uni-variate general linear model (GLM) (Yeon et al., 2017). Here, we conducted an in-depth investigation on neural correlates of sticky sensations by employing a multivoxel pattern analysis (MVPA) on the same dataset. In particular, we statistically compared multi-variate neural activities in response to the three groups of sticky stimuli: A supra-threshold group including a set of sticky stimuli that evoked vivid sticky perception; an infra-threshold group including another set of sticky stimuli that barely evoked sticky perception; and a sham group including acrylic stimuli with no physically sticky property. Searchlight MVPAs were performed to search for local activity patterns carrying neural information of stickiness perception. Similar to the uni-variate GLM results, significant multi-variate neural activity patterns were identified in postcentral gyrus, subcortical (basal ganglia and thalamus), and insula areas (insula and adjacent areas). Moreover, MVPAs revealed that activity patterns in posterior parietal cortex discriminated the perceptual intensities of stickiness, which was not present in the uni-variate analysis. Next, we applied a principal component analysis (PCA) to the voxel response patterns within identified clusters so as to find low-dimensional neural representations of stickiness intensities. Follow-up clustering analyses clearly showed separate neural grouping configurations between the Supra- and Infra-threshold groups. Interestingly, this neural categorization was in line with the perceptual grouping pattern obtained from the psychophysical data. Our findings thus suggest that different stickiness intensities would elicit distinct neural activity patterns in the human brain and may provide a neural basis for the perception and categorization of tactile stickiness. PMID:28936171

Human red cell 2,3-diphosphoglycerate mutase and monophosphoglycerate mutase: genetic evidence for two separate loci.

PubMed Central

Chen, S H; Anderson, J E; Giblett, E R

1977-01-01

Rare genetic variants of human red cell 2,3-diphosphoglycerate mutase (DPGM) and monophosphoglycerate mutase (MPGM) were compared by starch gel electrophoresis. The isozyme patterns showed that genetic variation of the enzymes were independent from each other, thus DPGM and MPGM must be controlled by two separate loci. Images Fig. 1 PMID:195467

Characteristics and Antitumor Activity of Morchella esculenta Polysaccharide Extracted by Pulsed Electric Field

PubMed Central

Liu, Chao; Sun, Yonghai; Mao, Qian; Guo, Xiaolei; Li, Peng; Liu, Yang; Xu, Na

2016-01-01

Polysaccharides from Morchella esculenta have been proven to be functional and helpful for humans. The purpose of this study was to investigate the chemical structure and anti-proliferating and antitumor activities of a Morchella esculenta polysaccharide (MEP) extracted by pulsed electric field (PEF) in submerged fermentation. The endo-polysaccharide was separated and purified by column chromatography and Gel permeation chromatography, and analyzed by gas chromatography. The MEP with an average molecular weight of 81,835 Da consisted of xylose, glucose, mannose, rhamnose and galactose at the ratio of 5.4:5.0:6.5:7.8:72.3. Structure of MEP was further analyzed by Fourier-transform infrared spectroscopy and 1H and 13C liquid-state nuclear magnetic resonance spectroscopy. Apoptosis tests proved that MEP could inhibit the proliferation and growth of human colon cancer HT-29 cells in a time- and dose-dependent manner within 48 h. This study provides more information on chemical structure of anti-proliferating polysaccharides isolated from Morchella esculenta. PMID:27338370

Telemetric recordings of single neuron activity and visual scenes in monkeys walking in an open field.

PubMed

Lei, Yanlin; Sun, Ninglei; Wilson, Fraser A W; Wang, Xiusong; Chen, Nanhui; Yang, Jianzhen; Peng, Yanping; Wang, Jianhong; Tian, Shaohua; Wang, Maohua; Miao, Yingda; Zhu, Weina; Qi, Hua; Ma, Yuanye

2004-05-30

This paper describes a portable recording system and methods for obtaining chronic recordings of single units and tracking rhesus monkey behavior in an open field. The integrated system consists of four major components: (1) microelectrode assembly; (2) head-stage; (3) recording station; and (4) data storage station, the first three of which are carried by the monkey and weigh 800 g. Our system provides synchronized video and electrophysiological signals, which are transmitted by a wireless system to a distance of 50 m. Its major advantages are that neuronal recordings are made in freely moving monkeys, and well-separated action potentials with amplitude five times higher than the background noise are usually recorded and readily kept for many hours. Using this system, we were able to study "place cells" in non-human primate brains. The described methods provide a new way to examine correlations between single neuron activity and primate behaviors, and can also be used to study the cellular basis of social behaviors in non-human primates.

Joint Spacelab-J (SL-J) Activities at the Huntsville Operations Support Center (HOSC) Spacelab

NASA Technical Reports Server (NTRS)

1999-01-01

The science laboratory, Spacelab-J (SL-J), flown aboard the STS-47 flight was a joint venture between NASA and the National Space Development Agency of Japan (NASDA) utilizing a manned Spacelab module. The mission conducted 24 materials science and 20 life science experiments, of which 35 were sponsored by NASDA, 7 by NASA, and two collaborative efforts. Materials science investigations covered such fields as biotechnology, electronic materials, fluid dynamics and transport phenomena, glasses and ceramics, metals and alloys, and acceleration measurements. Life sciences included experiments on human health, cell separation and biology, developmental biology, animal and human physiology and behavior, space radiation, and biological rhythms. Test subjects included the crew, Japanese koi fish (carp), cultured animal and plant cells, chicken embryos, fruit flies, fungi and plant seeds, and frogs and frog eggs. Featured together in joint ground activities during the SL-J mission are NASA/NASDA personnel at the Huntsville Operations Support Center (HOSC) Spacelab Payload Operations Control Center (SL POCC) at Marshall Space Flight Center (MSFC).

New activity pattern in human interactive dynamics

NASA Astrophysics Data System (ADS)

Formentin, Marco; Lovison, Alberto; Maritan, Amos; Zanzotto, Giovanni

2015-09-01

We investigate the response function of human agents as demonstrated by written correspondence, uncovering a new pattern for how the reactive dynamics of individuals is distributed across the set of each agent’s contacts. In long-term empirical data on email, we find that the set of response times considered separately for the messages to each different correspondent of a given writer, generate a family of heavy-tailed distributions, which have largely the same features for all agents, and whose characteristic times grow exponentially with the rank of each correspondent. We furthermore show that this new behavioral pattern emerges robustly by considering weighted moving averages of the priority-conditioned response-time probabilities generated by a basic prioritization model. Our findings clarify how the range of priorities in the inputs from one’s environment underpin and shape the dynamics of agents embedded in a net of reactive relations. These newly revealed activity patterns might be universal, being present in other general interactive environments, and constrain future models of communication and interaction networks, affecting their architecture and evolution.

Combination of aspartic acid and glutamic acid inhibits tumor cell proliferation.

PubMed

Yamaguchi, Yoshie; Yamamoto, Katsunori; Sato, Yoshinori; Inoue, Shinjiro; Morinaga, Tetsuo; Hirano, Eiichi

2016-01-01

Placental extract contains several biologically active compounds, and pharmacological induction of placental extract has therapeutic effects, such as improving liver function in patients with hepatitis or cirrhosis. Here, we searched for novel molecules with an anti-tumor activity in placental extracts. Active molecules were separated by chromatographic analysis, and their antiproliferative activities were determined by a colorimetric assay. We identified aspartic acid and glutamic acid to possess the antiproliferative activity against human hepatoma cells. Furthermore, we showed that the combination of aspartic acid and glutamic acid exhibited enhanced antiproliferative activity, and inhibited Akt phosphorylation. We also examined in vivo tumor inhibition activity using the rabbit VX2 liver tumor model. The treatment mixture (emulsion of the amino acids with Lipiodol) administered by hepatic artery injection inhibited tumor cell growth of the rabbit VX2 liver. These results suggest that the combination of aspartic acid and glutamic acid may be useful for induction of tumor cell death, and has the potential for clinical use as a cancer therapeutic agent.

Functional activities of acidic isoferritins and lactoferrin in vitro and in vivo.

PubMed

Broxmeyer, H E; Gentile, P; Cooper, S; Lu, L; Juliano, L; Piacibello, W; Meyers, P A; Cavanna, F

1984-01-01

The functional activities of acidic isoferritins (AIF) and lactoferin (LF) were evaluated. The inhibitory activity of AIF (AIFIA) was inactivated by preincubation with a monoclonal antibody (2A4) against AIF, but AIFIA was not inactivated by another monoclonal antibody against AIF (1C5), by a monoclonal antibody (3A5) against basic isoferritins, or by a heteroantiserum (LFT) against basic isoferritins. Monoclonal 2A4 also inactivated the inhibitory activity against colony formation by granulocyte-macrophage (CFU-GM) progenitor cells that was constitutively released by human monocytes or induced by human monocytes in the presence of OKT4+ lymphocytes. In addition to OKT4+ lymphocytes, the release of AIFIA from human monocytes was modulated by iron-saturated human LF and OKT8+ lymphocytes, both of which suppressed the release of AIFIA. Evidence for the physiologic relevance of AIF as a regulator of myelopoiesis was presented, in that human AIF suppressed the numbers of CFU-GM, BFU-E, and CFU-GEMM per femur and the cycling status of these cells in mice recovering from a sublethal dosage of Cytoxan. Abnormalities in LF and AIF interactions were found with cells from a pediatric patient with neutrophilia of unknown etiology that were consistent with the disease manifestations of neutrophilia. Polymorphonuclear neutrophils (PMN) from the patient contained low levels (1%-10% of control) of immunologically reactive LF and the LF found was ineffective as a suppressor molecule for the release of GM-CSF from normal mononuclear blood cells. In addition, the patient's GM-CSF releasing mononuclear blood cells were insensitive to the suppressive effects of purified LF, and colony formation by the patient's CFU-GM, but not BFU-E or CFU-GEMM, were insensitive to the suppressive effects of purified AIF. When the activity of purified AIF was assessed against mouse bone marrow cells under serum-free conditions, it was apparent that serum was not needed for the suppressive activity of AIF and that in some cases, serum actually masked the effects of AIF. Human monoblast cell line U937 was found to be a good model in vitro for the actions of LF and AIF; U937 cells induced for Ia-antigens by human gamma interferon were separated into populations of Ia-antigen+ and Ia-antigen- cells by fluorescence activated cell sorting (FACS), and LF and AIF suppressed colony formation only by the Ia-antigen+ U937 cells. A comparative analysis of bovine and human LF against release of GM-CSF from human mononuclear cells demonstrated that both were active in their iron-saturated form.(ABSTRACT TRUNCATED AT 400 WORDS)

Extracellular matrix proteins in healthy and retained placentas, comparing hemochorial and synepitheliochorial placentas.

PubMed

Franczyk, M; Lopucki, M; Stachowicz, N; Morawska, D; Kankofer, M

2017-02-01

The placenta expresses structural and biologically active proteins. Their synthesis is mainly regulated by genomic or nongenomic signals and modulated by hormones. These protein profiles are altered during different stages of pregnancy. The biological properties of extracellular matrix (ECM) proteins were defined and described in a number of tissues including placenta. These properties enable them to be the main players in the processes of attachment or invasion into the endometrium during initial placenta formation and its timely separation after delivery and detachment. In this review, we focused on the role of ECM proteins during attachment of the placenta to the uterine wall, its timely separation, and the implications of this process on retained or pathologically attached placenta. Although the amount of published information in this area is relatively scant, some of the key proteins and processes are well defined. We focused on the available data detailing the ECM protein profiles of human (histologically thin; hemochorial) and bovine (histologically thick; epitheliochorial) placentas and compared the shared and unique ECM proteins that are relevant to placental attachment and separation. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Identification of Env-specific monoclonal antibodies from Chinese HIV-1 infected person by magnetic beads separating B cells and single cell RT-PCR cloning].

PubMed

Huang, Xiang-Ying; Yu, Shuang-Qing; Cheng, Zhan; Ye, Jing-Rong; Xu, Ke; Feng, Xia; Zeng, Yi

2013-04-01

To establish a simple and practical method for screening of Env-specific monoclonal antibodies from HIV-1 infected individuals. Human B cells were purified by negative sorting from PBMCs and memory B cells were further enriched using anti-CD27 microbeads. Gp120 antigen labbled with biotin was incubated with memory B cells to specifically bind IgG on cells membrane. The memory B cells expressing the Env-specific antibody were harvested by magnetic beads separating, counted and diluted to the level of single cell in each PCR well that loading with catch buffer containing RNase inhibitor to get RNAs. The antibody genes were amplified by single cell RT-PCR and nested PCR, cloned into eukaryotic expression vectors and transfected into 293T cells. The binding activity of recombinant antibodies to Env were tested by ELISA. Three monocolonal Env-specific antibodies were isolated from one HIV-1 infected individual. We can obtain Env-specific antibody by biotin labbled antigen, magnetic beads separating technique coupled with single cell RT-PCR and expression cloning.

Health care and human rights: against the split duty gambit.

PubMed

Sreenivasan, Gopal

2016-08-01

There are various grounds on which one may wish to distinguish a right to health care from a right to health. In this article, I review some old grounds before introducing some new grounds. But my central task is to argue that separating a right to health care from a right to health has objectionable consequences. I offer two main objections. The domestic objection is that separating the two rights prevents the state from fulfilling its duty to maximise the health it provides each citizen from its fixed health budget. The international objection is that separating a human right to health care fails the moral requirement that, for any given moral human right, the substance to which any two right-holders are entitled be of an equal standard.

21 CFR 862.2230 - Chromatographic separation material for clinical use.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Chromatographic separation material for clinical... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2230 Chromatographic separation material for clinical use. (a) Identification. A...

Measurement of flow separation in a human vocal folds model

NASA Astrophysics Data System (ADS)

Šidlof, Petr; Doaré, Olivier; Cadot, Olivier; Chaigne, Antoine

2011-07-01

The paper provides experimental data on flow separation from a model of the human vocal folds. Data were measured on a four times scaled physical model, where one vocal fold was fixed and the other oscillated due to fluid-structure interaction. The vocal folds were fabricated from silicone rubber and placed on elastic support in the wall of a transparent wind tunnel. A PIV system was used to visualize the flow fields immediately downstream of the glottis and to measure the velocity fields. From the visualizations, the position of the flow separation point was evaluated using a semiautomatic procedure and plotted for different airflow velocities. The separation point position was quantified relative to the orifice width separately for the left and right vocal folds to account for flow asymmetry. The results indicate that the flow separation point remains close to the narrowest cross-section during most of the vocal fold vibration cycle, but moves significantly further downstream shortly prior to and after glottal closure.

Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects

NASA Astrophysics Data System (ADS)

Tripathi, Siddhartha; Kumar, Y. V. Balavarun; Agrawal, Amit; Prabhakar, Amit; Joshi, Suhas S.

2016-06-01

In this research work, we present a simple and efficient passive microfluidic device for plasma separation from pure blood. The microdevice has been fabricated using conventional photolithography technique on a single layer of polydimethylsiloxane, and has been extensively tested on whole blood and enhanced (upto 62%) hematocrit levels of human blood. The microdevice employs elevated dimensions of about 100 μm such elevated dimensions ensure clog-free operation of the microdevice and is relatively easy to fabricate. We show that our microdevice achieves almost 100% separation efficiency on undiluted blood in the flow rate range of 0.3 to 0.5 ml/min. Detailed biological characterization of the plasma obtained from the microdevice is carried out by testing: proteins by ultra-violet spectrophotometric method, hCG (human chorionic gonadotropin) hormone, and conducting random blood glucose test. Additionally, flow cytometry study has also been carried on the separated plasma. These tests attest to the high quality of plasma recovered. The microdevice developed in this work is an outcome of extensive experimental research on understanding the flow behavior and separation phenomenon of blood in microchannels. The microdevice is compact, economical and effective, and is particularly suited in continuous flow operations.

Develop Recovery Systems for Separations of Salts from Process Streams for use in Advanced Life Support System

NASA Technical Reports Server (NTRS)

Colon, Guillermo

1998-01-01

The main objectives of this project were the development of a four-compartment electrolytic cell using high selective membranes to remove nitrate from crop residue leachate and convert it to nitric acid, and the development of an six compartment electrodialysis cell to remove selectively sodium from urine wastes. The recovery of both plant inedible biomass and human wastes nutrients to sustain a biomass production system are important aspects in the development of a controlled ecological life support system (CELSS) to provide the basic human needs required for life support during long term space missions. A four-compartment electrolytic cell has been proposed to remove selectively nitrate from crop residue and to convert it to nitric acid, which is actually used in the NASA-KSC Controlled Ecological Life Support System to control the pH of the aerobic bioreactors and biomass production chamber. Human activities in a closed system require large amount of air, water and minerals to sustain life and also generate wastes. Before using human wastes as nutrients, these must be treated to reduce organic content and to remove some minerals which have adverse effects on plant growth. Of all the minerals present in human urine, sodium chloride (NACl) is the only one that can not be used as nutrient for most plants. Human activities also requires sodium chloride as part of the diet. Therefore, technology to remove and recover sodium chloride from wastes is highly desirable. A six-compartment electrodialysis cell using high selective membranes has been proposed to remove and recover NaCl from human urine.

Molecular cloning, characterization, and expression of human ADP-ribosylation factors: Two guanine nucleotide-dependent activators of cholera toxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bobak, D.A.; Nightingale, M.S.; Murtagh, J.J.

1989-08-01

ADP-ribosylation factors (ARFs) are small guanine nucleotide-binding proteins that enhance the enzymatic activities of cholera toxin. Two ARF cDNAs, ARF1 and ARF3, were cloned from a human cerebellum library. Based on deduced amino acid sequences and patterns of hybridization of cDNA and oligonucleotide probes with mammalian brain poly(A){sup +} RNA, human ARF1 is the homologue of bovine ARF1. Human ARF3, which differs from bovine ARF1 and bovine ARF2, appears to represent a newly identified third type of ARF. Hybridization patterns of human ARF cDNA and clone-specific oligonucleotides with poly(A){sup +} RNA are consistent with the presence of at least two,more » and perhaps four, separate ARF messages in human brain. In vitro translation of ARF1, ARF2, and ARF3 produced proteins that behaved, by SDS/PAGE, similar to a purified soluble brain ARF. Deduced amino acid sequences of human ARF1 and ARF3 contain regions, similar to those in other G proteins, that are believed to be involved in GTP binding and hydrolysis. ARFS also exhibit a modest degree of homology with a bovine phospholipase C. The observations reported here support the conclusion that the ARFs are members of a multigene family of small guanine nucleotide-binding proteins. Definition of the regulation of ARF mRNAs and of function(s) of recombinant ARF proteins will aid in the elucidation of the physiologic role(s) of ARFs.« less

Isolation and characterization of bioactive components from Mirabilis jalapa L. radix

PubMed Central

Gogoi, Jyotchna; Nakhuru, Khonamai Sewa; Policegoudra, Rudragoud S.; Chattopadhyay, Pronobesh; Rai, Ashok Kumar; Veer, Vijay

2015-01-01

The present investigation was carried out to isolate and characterize bioactive components from Mirabilis jalapa L. radix (紫茉莉根 zǐ mò lì gēn). Thin-layer chromatography was used for the separation of spots from fractions of the crude extract. Separated spots were collected for identification of their activities. Free-radical scavenging activity was evaluated by spraying thin-layer chromatography plates (spotted with fractions) with 0.2% of 2,2-diphenyl-1-picrylhydrazyl solution. Activity against human pathogens such as Staphylococcus aureus and Candida albicans were determined using the agar diffusion method. Potential spots were subjected to infrared (IR) analysis and gas chromatography for characterization. Two spots (5F1 and 1F3) showed free-radical scavenging activity. The 1F3 spot was active against both S. aureus and C. albicans, whereas the 5F1 spot was active against S. aureus only. IR spectral analysis indicated that 5F1 spot to be a triterpenoid. Using IR spectral analysis and an IR library search, the 1F3 spot was identified to be a flavone, which may have a hydroxyl group in ring “A” of the flavone nucleus. Our results indicated that the 1F3 and 5F1 spots are potential free-radical scavengers. Both 1F3 and 5F1 exhibited antimicrobial activity. IR spectral analysis coupled with an IR library search indicated 1F3 and 5F1 to be a flavone and a triterpenoid, respectively. PMID:26870679

Not one extrastriate body area: Using anatomical landmarks, hMT+, and visual field maps to parcellate limb-selective activations in human lateral occipitotemporal cortex

PubMed Central

Weiner, Kevin S.; Grill-Spector, Kalanit

2011-01-01

The prevailing view of human lateral occipitotemporal cortex (LOTC) organization suggests a single area selective for images of the human body (extrastriate body area, EBA) that highly overlaps with the human motion-selective complex (hMT+). Using functional magnetic resonance imaging with higher resolution (1.5mm voxels) than past studies (3–4mm voxels), we examined the fine-scale spatial organization of these activations relative to each other, as well as to visual field maps in LOTC. Rather than one contiguous EBA highly overlapping hMT+, results indicate three limb-selective activations organized in a crescent surrounding hMT+: (1) an activation posterior to hMT+ on the lateral occipital sulcus/middle occipital gyrus (LOS/MOG) overlapping the lower vertical meridian shared between visual field maps LO-2 and TO-1, (2) an activation anterior to hMT+ on the middle temporal gyrus (MTG) consistently overlapping the lower vertical meridian of TO-2 and extending outside presently defined visual field maps, and (3) an activation inferior to hMT+ on the inferotemporal gyrus (ITG) overlapping the parafoveal representation of the TO cluster. This crescent organization of limb-selective activations surrounding hMT+ is reproducible over a span of three years and is consistent across different image types used for localization. Further, these regions exhibit differential position properties: preference for contralateral image presentation decreases and preference for foveal presentation increases from the limb-selective LOS to the MTG. Finally, the relationship between limb-selective activations and visual field maps extends to the dorsal stream where a posterior IPS activation overlaps V7. Overall, our measurements demonstrate a series of LOTC limb-selective activations that 1) have separate anatomical and functional boundaries, 2) overlap distinct visual field maps, and 3) illustrate differential position properties. These findings indicate that category selectivity alone is an insufficient organization principle for defining brain areas. Instead, multiple properties are necessary in order to parcellate and understand the functional organization of high-level visual cortex. PMID:21439386

Yellowstone bison genetics: let us move forward

USGS Publications Warehouse

Halbert, Natalie D.; Gogan, Peter J.P.; Hedrick, Philip W.; Wahl, Jacquelyn M.; Derr, James N.

2012-01-01

White and Wallen (2012) disagree with the conclusions and suggestions made in our recent assessment of population structure among Yellowstone National Park (YNP) bison based on 46 autosomal microsatellite loci in 661 animals (Halbert et al. 2012). First, they suggest that "the existing genetic substructure (that we observed) was artificially created." Specifically, they suggest that the substructure observed between the northern and central populations is the result of human activities, both historical and recent. In fact, the genetic composition of all known existing bison herds was created by, or has been influenced by, anthropogenic activities, although this obviously does not reduce the value of these herds for genetic conservation (Dratch and Gogan 2010). As perspective, many, if not most, species of conservation concern have been influenced by human actions and as a result currently exist as isolated populations. However, it is quite difficult to distinguish between genetic differences caused by human actions and important ancestral variation contained in separate populations without data from early time periods. Therefore, to not lose genetic variation that may be significant or indicative of important genetic variation, the generally acceptable management approach is to attempt to retain this variation based on the observed population genetic subdivision (Hedrick et al. 1986).

Towards nanoscale biomedical devices in medicine: biofunctional and spectroscopic characterization of superparamagnetic nanoparticles.

PubMed

Parracino, Antonietta; Gajula, Gnana Prakash; di Gennaro, Ane Kold; Neves-Petersen, Maria Teresa; Rafaelsen, Jens; Petersen, Steffen B

2011-03-01

Medical interest in nanotechnology originates from a belief that nanoscale therapeutic devices can be constructed and directed towards its target inside the human body. Such nanodevices can be engineered by coupling superparamagnetic nanoparticle to biomedically active proteins. We hereby report the immobilization of a PhEst, a S-formylglutathione hydrolase from the psychrophilic P. haloplanktis TAC125 onto the gold coated surface of modified superparamagnetic core-shell nanoparticles (Fe(3)O(4)@Au). The synthesis of the nanoparticles is also reported. S-formylglutathione hydrolases constitute a family of ubiquitous enzymes which play a key role in formaldehyde detoxification both in prokaryotes and eukaryotes. PhEst was originally annotated as a putative feruloyl esterase, an enzyme that releases ferulic acid (an antioxidant reactive towards free radicals such as reactive oxygen species) from polysaccharides esters. Dynamic light scattering, scanning electron microscopy with energy dispersive X-ray spectroscopy, UV-visible absorption spectroscopy, fluorescence spectroscopy, magnetic separation technique and enzyme catalytic assay confirmed the chemical composition of the gold covered superparamagnetic nanoparticles, the binding and activity of the enzyme onto the nanoparticles. Activity data in U/ml confirmed that the immobilized enzyme is approximately 2 times more active than the free enzyme in solution. Such particles can be directed with external magnetic fields for bio-separation and focused towards a medical target for therapeutical as well as bio-sensor applications. © Springer Science+Business Media, LLC 2010

Separation of large mammalian ventricular myosin differing in ATPase activity.

PubMed

Rupp, Heinz; Maisch, Bernhard

2007-01-01

To investigate a possible heterogeneity of human ventricular myosin, papillary muscles of patients with valvular dysfunction were examined using a modified native gel electrophoresis. Myosin was separated into 2 components termed VA and VB, whereby the VA to VB proportion appeared to depend on the ventricular load. The proportion of the faster migrating band VA was correlated (P<0.05) with end-diastolic pressure and the aortic pressure-cardiac index product. The regression based on these variables accounted for 67% of the variation in VA (R2=0.67). The VA proportion was, however, not significantly correlated with cardiac norepinephrine concentration. The ATPase activity of the 2 components of myosin was assessed from the Ca3(PO4)2 precipitation by incubating the gel in the presence of ATP and CaCl2. The ATPase activity of VA was 60% of that of VB. The VA and VB forms were observed also in the cat (31.4% VA), dog (32.1% VA), pig (28.5% VA), wild pig (33.7% VA), and roe deer (30.5% VA). VA and VB were not detected in the rat exhibiting the 3 isoforms V1, V2, and V3, rabbit (100% V3), and hare (86% V1). The data demonstrate a heterogeneity of large mammalian ventricular myosin, whereby an increased cardiac load appeared to be associated with a higher myosin VA proportion that exhibited a reduced ATPase activity.

Using nonlocal means to separate cardiac and respiration sounds

NASA Astrophysics Data System (ADS)

Rudnitskii, A. G.

2014-11-01

The paper presents the results of applying nonlocal means (NLMs) approach in the problem of separating respiration and cardiac sounds in a signal recorded on a human chest wall. The performance of the algorithm was tested both by simulated and real signals. As a quantitative efficiency measure of NLM filtration, the angle of divergence between isolated and reference signal was used. It is shown that for a wide range of signal-to-noise ratios, the algorithm makes it possible to efficiently solve this problem of separating cardiac and respiration sounds in the sum signal recorded on a human chest wall.

Physical Human Activity Recognition Using Wearable Sensors.

PubMed

Attal, Ferhat; Mohammed, Samer; Dedabrishvili, Mariam; Chamroukhi, Faicel; Oukhellou, Latifa; Amirat, Yacine

2015-12-11

This paper presents a review of different classification techniques used to recognize human activities from wearable inertial sensor data. Three inertial sensor units were used in this study and were worn by healthy subjects at key points of upper/lower body limbs (chest, right thigh and left ankle). Three main steps describe the activity recognition process: sensors' placement, data pre-processing and data classification. Four supervised classification techniques namely, k-Nearest Neighbor (k-NN), Support Vector Machines (SVM), Gaussian Mixture Models (GMM), and Random Forest (RF) as well as three unsupervised classification techniques namely, k-Means, Gaussian mixture models (GMM) and Hidden Markov Model (HMM), are compared in terms of correct classification rate, F-measure, recall, precision, and specificity. Raw data and extracted features are used separately as inputs of each classifier. The feature selection is performed using a wrapper approach based on the RF algorithm. Based on our experiments, the results obtained show that the k-NN classifier provides the best performance compared to other supervised classification algorithms, whereas the HMM classifier is the one that gives the best results among unsupervised classification algorithms. This comparison highlights which approach gives better performance in both supervised and unsupervised contexts. It should be noted that the obtained results are limited to the context of this study, which concerns the classification of the main daily living human activities using three wearable accelerometers placed at the chest, right shank and left ankle of the subject.

Physical Human Activity Recognition Using Wearable Sensors

PubMed Central

Attal, Ferhat; Mohammed, Samer; Dedabrishvili, Mariam; Chamroukhi, Faicel; Oukhellou, Latifa; Amirat, Yacine

2015-01-01

This paper presents a review of different classification techniques used to recognize human activities from wearable inertial sensor data. Three inertial sensor units were used in this study and were worn by healthy subjects at key points of upper/lower body limbs (chest, right thigh and left ankle). Three main steps describe the activity recognition process: sensors’ placement, data pre-processing and data classification. Four supervised classification techniques namely, k-Nearest Neighbor (k-NN), Support Vector Machines (SVM), Gaussian Mixture Models (GMM), and Random Forest (RF) as well as three unsupervised classification techniques namely, k-Means, Gaussian mixture models (GMM) and Hidden Markov Model (HMM), are compared in terms of correct classification rate, F-measure, recall, precision, and specificity. Raw data and extracted features are used separately as inputs of each classifier. The feature selection is performed using a wrapper approach based on the RF algorithm. Based on our experiments, the results obtained show that the k-NN classifier provides the best performance compared to other supervised classification algorithms, whereas the HMM classifier is the one that gives the best results among unsupervised classification algorithms. This comparison highlights which approach gives better performance in both supervised and unsupervised contexts. It should be noted that the obtained results are limited to the context of this study, which concerns the classification of the main daily living human activities using three wearable accelerometers placed at the chest, right shank and left ankle of the subject. PMID:26690450

An fMRI study of the brain responses of traumatized mothers to viewing their toddlers during separation and play

PubMed Central

Moser, Dominik A.; Wang, Zhishun; Marsh, Rachel; Hao, XueJun; Duan, Yunsuo; Yu, Shan; Gunter, Benjamin; Murphy, David; McCaw, Jaime; Kangarlu, Alayar; Willheim, Erica; Myers, Michael M.; Hofer, Myron A.; Peterson, Bradley S.

2012-01-01

This study tested whether mothers with interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) vs healthy controls (HC) would show greater limbic and less frontocortical activity when viewing young children during separation compared to quiet play. Mothers of 20 children (12–42 months) participated: 11 IPV-PTSD mothers and 9 HC with no PTSD. During fMRI, mothers watched epochs of play and separation from their own and unfamiliar children. The study focused on comparison of PTSD mothers vs HC viewing children in separation vs play, and viewing own vs unfamiliar children in separation. Both groups showed distinct patterns of brain activation in response to viewing children in separation vs play. PTSD mothers showed greater limbic and less frontocortical activity (BA10) than HC. PTSD mothers also reported feeling more stressed than HC when watching own and unfamiliar children during separation. Their self-reported stress was associated with greater limbic and less frontocortical activity. Both groups also showed distinct patterns of brain activation in response to viewing their own vs unfamiliar children during separation. PTSD mothers’ may not have access to frontocortical regulation of limbic response upon seeing own and unfamiliar children in separation. This converges with previously reported associations of maternal IPV-PTSD and atypical caregiving behavior following separation. PMID:22021653

Rapid cell separation with minimal manipulation for autologous cell therapies

NASA Astrophysics Data System (ADS)

Smith, Alban J.; O'Rorke, Richard D.; Kale, Akshay; Rimsa, Roberts; Tomlinson, Matthew J.; Kirkham, Jennifer; Davies, A. Giles; Wälti, Christoph; Wood, Christopher D.

2017-02-01

The ability to isolate specific, viable cell populations from mixed ensembles with minimal manipulation and within intra-operative time would provide significant advantages for autologous, cell-based therapies in regenerative medicine. Current cell-enrichment technologies are either slow, lack specificity and/or require labelling. Thus a rapid, label-free separation technology that does not affect cell functionality, viability or phenotype is highly desirable. Here, we demonstrate separation of viable from non-viable human stromal cells using remote dielectrophoresis, in which an electric field is coupled into a microfluidic channel using shear-horizontal surface acoustic waves, producing an array of virtual electrodes within the channel. This allows high-throughput dielectrophoretic cell separation in high conductivity, physiological-like fluids, overcoming the limitations of conventional dielectrophoresis. We demonstrate viable/non-viable separation efficacy of >98% in pre-purified mesenchymal stromal cells, extracted from human dental pulp, with no adverse effects on cell viability, or on their subsequent osteogenic capabilities.

SEPARATION AND CHARACTERIZATION OF HUMAN SERUM CHYLOMICRONS

PubMed Central

Scanu, Angelo; Page, Irvine H.

1959-01-01

Chylomicrons were separated by low and high speed ultracentrifugation from lipemic sera of human subjects in the absorptive phase. The final chylomicron preparation was free from other serum components and contained a small constant amount of protein, approximately 2 per cent of the chylomicron fraction. Electrophoresis, immunochemical analysis, and absorption experiments identified the protein component as derived from a mixture of beta and alpha1 serum lipoproteins. Large aliquots of an emulsion of serum freed of chylomicrons and coconut oil were incubated at 37°C. for 2 hours and ultracentrifuged as in the preparation of chylomicrons. The fat particles now showed the presence of minute amounts of beta and alpha1 serum lipoproteins in almost the same proportion as found in chylomicrons. "Finger prints" of delipidized samples of chylomicrons and particles from serum-coconut oil emulsion gave similar, although not identical patterns. The data on "clearing factor" activity corroborated the finding that serum alpha1 lipoproteins are contained in chylomicrons and particles from serum-coconut oil emulsion. These two lipide particles, partially delipidized, were both able to activate a "clearing factor" system in vitro, a property exhibited only by intact or partially delipidized alpha1 serum lipoproteins. Clearing activity was satisfactorily determined by using an emulsion of coconut oil mixed in agar as a substrate to give an opaque gel, in which the diffusing enzyme showed its activity by areas of clearing. The results obtained by this technique were in agreement with those based on fall in optical density and non-esterified fatty acid production. Chemical analysis of serum chylomicrons showed a concentration of cholesterol and phospholipides higher than could be accounted for by the attached beta and alpha1 serum lipoproteins. On the basis of these results the assumption is made that in the blood stream small amounts of serum lipoproteins, by a process of adsorption, form a complex with the absorbed triglycerides, cholesterol, and phospholipides, to produce chylomicrons. PMID:13620852

Voluntary Movement Frequencies in Submaximal One- and Two-Legged Knee Extension Exercise and Pedaling

PubMed Central

Stang, Julie; Wiig, Håvard; Hermansen, Marte; Hansen, Ernst Albin

2016-01-01

Understanding of behavior and control of human voluntary rhythmic stereotyped leg movements is useful in work to improve performance, function, and rehabilitation of exercising, healthy, and injured humans. The present study aimed at adding to the existing understanding within this field. To pursue the aim, correlations between freely chosen movement frequencies in relatively simple, single-joint, one- and two-legged knee extension exercise were investigated. The same was done for more complex, multiple-joint, one- and two-legged pedaling. These particular activities were chosen because they could be considered related to some extent, as they shared a key aspect of knee extension, and because they at the same time were different. The activities were performed at submaximal intensities, by healthy individuals (n = 16, thereof eight women; 23.4 ± 2.7 years; 1.70 ± 0.11 m; 68.6 ± 11.2 kg). High and fair correlations (R-values of 0.99 and 0.75) occurred between frequencies generated with the dominant leg and the nondominant leg during knee extension exercise and pedaling, respectively. Fair to high correlations (R-values between 0.71 and 0.95) occurred between frequencies performed with each of the two legs in an activity, and the two-legged frequency performed in the same type of activity. In general, the correlations were higher for knee extension exercise than for pedaling. Correlations between knee extension and pedaling frequencies were of modest occurrence. The correlations between movement frequencies generated separately by each of the legs might be interpreted to support the following working hypothesis, which was based on existing literature. It is likely that involved central pattern generators (CPGs) of the two legs share a common frequency generator or that separate frequency generators of each leg are attuned via interneuronal connections. Further, activity type appeared to be relevant. Thus, the apparent common rhythmogenesis for the two legs appeared to be stronger for the relatively simple single-joint activity of knee extension exercise as compared to the more complex multi-joint activity of pedaling. Finally, it appeared that the shared aspect of knee extension in the related types of activities of knee extension exercise and pedaling was insufficient to cause obvious correlations between generated movement frequencies in the two types of activities. PMID:26973486

Effects of Δ9-tetrahydrocannabinol administration on human encoding and recall memory function: a pharmacological FMRI study.

PubMed

Bossong, Matthijs G; Jager, Gerry; van Hell, Hendrika H; Zuurman, Lineke; Jansma, J Martijn; Mehta, Mitul A; van Gerven, Joop M A; Kahn, René S; Ramsey, Nick F

2012-03-01

Deficits in memory function are an incapacitating aspect of various psychiatric and neurological disorders. Animal studies have recently provided strong evidence for involvement of the endocannabinoid (eCB) system in memory function. Neuropsychological studies in humans have shown less convincing evidence but suggest that administration of cannabinoid substances affects encoding rather than recall of information. In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of Δ9-tetrahydrocannabinol (THC) inhalation on associative memory-related brain function in 13 healthy volunteers. Performance and brain activation during associative memory were assessed using a pictorial memory task, consisting of separate encoding and recall conditions. Administration of THC caused reductions in activity during encoding in the right insula, the right inferior frontal gyrus, and the left middle occipital gyrus and a network-wide increase in activity during recall, which was most prominent in bilateral cuneus and precuneus. THC administration did not affect task performance, but while during placebo recall activity significantly explained variance in performance, this effect disappeared after THC. These findings suggest eCB involvement in encoding of pictorial information. Increased precuneus activity could reflect impaired recall function, but the absence of THC effects on task performance suggests a compensatory mechanism. These results further emphasize the eCB system as a potential novel target for treatment of memory disorders and a promising target for development of new therapies to reduce memory deficits in humans.

Acceptability of risk from radiation: Application to human space flight

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

This one of NASA`s sponsored activities of the NCRP. In 1983, NASA asked NCRP to examine radiation risks in space and to make recommendations about career radiation limits for astronauts (with cancer considered as the principal risk). In conjunction with that effort, NCRP was asked to convene this symposium; objective is to examine the technical, strategic, and philosophical issues pertaining to acceptable risk and radiation in space. Nine papers are included together with panel discussions and a summary. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

THORON-SCOUT - first diffusion based active Radon and Thoron monitor

NASA Astrophysics Data System (ADS)

Wagner, W.; Streil, T.; Oeser, V.; Horak, G.; Duzynski, M.

2016-10-01

THORON-SCOUT is a stand-alone diffusion based active Radon and Thoron monitor for long term indoor measurements to evaluate the human health risk due to activity concentration in the breathing air. Alpha-particle spectroscopy of Po isotopes, being the progeny of the decay of the radioactive noble gas Radon, is applied to separately monitor activity contributions of 222Rn and 220Rn (Thoron) as well. In this work we show that the portion of Thoron (Tn) may locally be remarkable and even dominating and cannot be neglected as often has been assumed up to now. Along with tobacco consumption, Rn radioactivity turned out to be a dangerous cause of lung cancer, especially in older badly vented buildings situated in regions of radioactive geological formations. THORON-SCOUT allows a precise examination of the indoor atmosphere with respect to Rn and Inactivity concentration and, therefore, a realistic evaluation of corresponding health risk.

Distinct Pattern Separation Related Transfer Functions in Human CA3/Dentate and CA1 Revealed Using High-Resolution fMRI and Variable Mnemonic Similarity

ERIC Educational Resources Information Center

Lacy, Joyce W.; Yassa, Michael A.; Stark, Shauna M.; Muftuler, L. Tugan; Stark, Craig E. L.

2011-01-01

Producing and maintaining distinct (orthogonal) neural representations for similar events is critical to avoiding interference in long-term memory. Recently, our laboratory provided the first evidence for separation-like signals in the human CA3/dentate. Here, we extended this by parametrically varying the change in input (similarity) while…

The rapid and direct determination of ATP-ase activity by ion exchange chromatography and the application to the activity of heat shock protein-90

PubMed Central

Bartolini, Manuela; Wainer, Irving W.; Bertucci, Carlo; Andrisano, Vincenza

2012-01-01

Adenosine nucleotides are involved as substrates or co-factors in several biochemical reactions, catalyzed by enzymes, which modulate energy production, signal transduction and cell proliferation. We here report the development and optimization of an ion exchange liquid chromatography (LC) method for the determination of ATP, ADP and AMP. This method is specifically aimed at the determination of the ATP-ase activity of human heat shock protein 90 (Hsp90), a molecular chaperone that has emerged as target enzyme in cancer therapy. Separation of the three nucleotides was achieved in a 15-min run by using a disk shaped monolithic ethylene diamine stationary phase of small dimensions (2×6 mm i.d.), under a three-solvent gradient elution mode and UV detection at 256 nm. The described direct LC method resulted highly specific as a consequence of the baseline separation of the three adenosine nucleotides and could be applied to the determination of the enzymatic activity of ADP/ATP generating or consuming enzymes (such as kinases). Furthermore, comparison of the LOD and LOQ values of the LC method with those obtained with the malachite green assay, which is one of the most used indirect screening methodologies for ATP-ase activity, showed that the LC method has a similar range of application without presenting the drawbacks related to contamination by inorganic phosphate ions and glycerol, which are present in Hsp90 commercial samples. PMID:22497853

Fish Oil Supplementation in Humans: Effects on Platelet Responses, Phospholipid Composition and Metabolism.

NASA Astrophysics Data System (ADS)

Skeaff, Clark Murray

Platelets are believed to play a significant role in the development of occlusive vascular diseases. Epidemiological reports have correlated the high intake of marine foods, rich in omega3 fatty acids, with diminished platelet responses and a low incidence of arterial thrombosis and myocardial infarction. The activation of platelet responses is mediated by the accelerated metabolism of membrane phospholipid; therefore, it was of interest to examine, in human volunteers, the effect of a dietary fish oil concentrate (MaxEPA), enriched in omega 3 polyunsaturated fatty acids, on platelet aggregation and phospholipid composition/metabolism. For the complete separation of cellular phospholipids, a one-dimensional thin-layer chromatography system using silica-gel pre-coated glass plates was developed. The solvent system consisted of CHCl_3/CH_3OH/CH _3COOH/H_2O (50/37.5/3.5/2.0, by vol), required approximately 90-120 minutes for full phospholipid separation, and was highly reproducible even under conditions of variable humidity and temperature. The consumption of a fish oil concentrate (MaxEPA) for 6 weeks (3.6 g of 20:5omega 3 and 2.4 g of 22:6omega3 per day) diminished both the collagen- and platelet activating factor-induced maximum aggregation responses in washed human platelet suspensions by 50.1% and 27.2%, respectively, as compared to initial unsupplemented baseline responses. Thrombin -induced aggregation remained unchanged. Thrombin stimulation of intact human platelets produced a significant decrease in the mass of phosphatidylinositol in plasma membrane. In platelets pre-labelled with (2-^3H) glycerol and stimulated with either thrombin or low-dose collagen, the loss of (^3H) phosphatidylinositol did not differ between those subjects consuming olive oil or fish oil. Likewise, the thrombin-stimulated accumulation of diacylglycerol, an activator of protein kinase C, was unaffected by fish oil consumption. The ratio of collagen -induced increase in radioactivity associated with ( ^3H) PIP_2/( ^3H) PIP was 0.41 in fish oil consumers and 1.14 in olive oil consumers. These results are consistent with a dampened collagen-induced phosphatidylinositol 4 -phosphate kinase activity in platelets of healthy individuals consuming dietary fish oil. This effect may be eicosanoid -related based on work with BW 755C, a dual inhibitor of the cyclooxygenase and lipoxygenase enzymes. The relevance of these findings to the altered production of inositol 1,4,5 trisphosphate remains to be determined.

Quantitative transporter proteomics by liquid chromatography with tandem mass spectrometry: addressing methodologic issues of plasma membrane isolation and expression-activity relationship.

PubMed

Kumar, Vineet; Prasad, Bhagwat; Patilea, Gabriela; Gupta, Anshul; Salphati, Laurent; Evers, Raymond; Hop, Cornelis E C A; Unadkat, Jashvant D

2015-02-01

To predict transporter-mediated drug disposition using physiologically based pharmacokinetic models, one approach is to measure transport activity and relate it to protein expression levels in cell lines (overexpressing the transporter) and then scale these to via in vitro to in vivo extrapolation (IVIVE). This approach makes two major assumptions. First, that the expression of the transporter is predominantly in the plasma membrane. Second, that there is a linear correlation between expression level and activity of the transporter protein. The present study was conducted to test these two assumptions. We evaluated two commercially available kits that claimed to separate plasma membrane from other cell membranes. The Qiagen Qproteome kit yielded very little protein in the fraction purported to be the plasma membrane. The Abcam Phase Separation kit enriched the plasma membrane but did not separate it from other intracellular membranes. For the Abcam method, the expression level of organic anion-transporting polypeptides (OATP) 1B1/2B1 and breast cancer resistance protein (BCRP) proteins in all subcellular fractions isolated from cells or human liver tissue tracked that of Na⁺-K⁺ ATPase. Assuming that Na⁺-K⁺ ATPase is predominantly located in the plasma membrane, these data suggest that the transporters measured are also primarily located in the plasma membrane. Using short hairpin RNA, we created clones of cell lines with varying degrees of OATP1B1 or BCRP expression level. In these clones, transport activity of OATP1B1 or BCRP was highly correlated with protein expression level (r² > 0.9). These data support the use of transporter expression level data and activity data from transporter overexpressing cell lines for IVIVE of transporter-mediated disposition of drugs. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Isolation of osteoprogenitors from human jaw periosteal cells: a comparison of two magnetic separation methods.

PubMed

Olbrich, Marcus; Rieger, Melanie; Reinert, Siegmar; Alexander, Dorothea

2012-01-01

Human jaw periosteum tissue contains osteoprogenitors that have potential for tissue engineering applications in oral and maxillofacial surgeries. To isolate osteoprogenitor cells from heterogeneous cell populations, we used the specific mesenchymal stem cell antigen-1 (MSCA-1) antibody and compared two magnetic separation methods. We analyzed the obtained MSCA-1(+) and MSCA-1(-) fractions in terms of purity, yield of positive/negative cells and proliferative and mineralization potentials. The analysis of cell viability after separation revealed that the EasySep method yielded higher viability rates, whereas the flow cytometry results showed a higher purity for the MACS-separated cell fractions. The mineralization capacity of the osteogenic induced MSCA-1(+) cells compared with the MSCA-1(-) controls using MACS was 5-fold higher, whereas the same comparison after EasySep showed no significant differences between both fractions. By analyzing cell proliferation, we detected a significant difference between the proliferative potential of the osteogenic cells versus untreated cells after the MACS and EasySep separations. The differentiated cells after MACS separation adjusted their proliferative capacity, whereas the EasySep-separated cells failed to do so. The protein expression analysis showed small differences between the two separation methods. Our findings suggest that MACS is a more suitable separation method to isolate osteoprogenitors from the entire jaw periosteal cell population.

[Purification of human goose-type lysozyme 2 (HLysG2) from human seminal plasma and analysis of its enzymatic properties].

PubMed

Huang, Peng; Yang, Zhifang; Bao, Jianying; Zhang, Ning; Li, Wenshu

2017-03-01

Objective To purify human goose-type lysozyme 2 (HLysG2) from human seminal plasma by chromatography and analyze its enzymatic properties. Methods The distribution of HLysG2 in semen was analyzed by Western blot analysis. Seminal plasma was subjected to the separation of target protein using cation-exchange chromatography, chitin affinity chromatography and size-exclusion chromatography. The purified product was identified by Western blot analysis and mass spectrometry (MS).The purity was analyzed by high performance liquid chromatography (HPLC). Then, the optimum pH, ion concentration and temperature of HLysG2 and its standard activity were determined by the turbidimetric assay. The bactericidal activity of HLysG2 was assessed by the colony-forming assay. Results The existence of HLysG2 in seminal plasma was confirmed by Western blot analysis. A protein of about 21.5 kDa was purified from seminal plasma by the three kinds of chromatography and identified as HLysG2 by Western blot analysis and MS. The final purity of the purified product was above 99.0% and the peak enzymatic activity reached 13 800 U/mg under the condition of pH 6.4, 0.09 mol/L Na + , 30DegreesCelsius. In vitro assay indicated that HLysG2 had a significant killing effect on Micrococcus lysodeikticus, Bacillus subtilis and Staphylococcus aureus, but not on Pseudomonas aeruginosa and Escherichia coli. Conclusion Native HLysG2 can be obtained from seminal plasma by chromatography. It has in vitro bactericidal activity against Gram-positive bacteria, suggesting that it might play a role in innate immunity of the male reproductive system.

Cellular STAT3 functions via PCBP2 to restrain Epstein-Barr Virus lytic activation in B lymphocytes.

PubMed

Koganti, Siva; Clark, Carissa; Zhi, Jizu; Li, Xiaofan; Chen, Emily I; Chakrabortty, Sharmistha; Hill, Erik R; Bhaduri-McIntosh, Sumita

2015-05-01

A major hurdle to killing Epstein-Barr virus (EBV)-infected tumor cells using oncolytic therapy is the presence of a substantial fraction of EBV-infected cells that does not support the lytic phase of EBV despite exposure to lytic cycle-promoting agents. To determine the mechanism(s) underlying this refractory state, we developed a strategy to separate lytic from refractory EBV-positive (EBV(+)) cells. By examining the cellular transcriptome in separated cells, we previously discovered that high levels of host STAT3 (signal transducer and activator of transcription 3) curtail the susceptibility of latently infected cells to lytic cycle activation signals. The goals of the present study were 2-fold: (i) to determine the mechanism of STAT3-mediated resistance to lytic activation and (ii) to exploit our findings to enhance susceptibility to lytic activation. We therefore analyzed our microarray data set, cellular proteomes of separated lytic and refractory cells, and a publically available STAT3 chromatin immunoprecipitation sequencing (ChIP-Seq) data set to identify cellular PCBP2 [poly(C)-binding protein 2], an RNA-binding protein, as a transcriptional target of STAT3 in refractory cells. Using Burkitt lymphoma cells and EBV(+) cell lines from patients with hypomorphic STAT3 mutations, we demonstrate that single cells expressing high levels of PCBP2 are refractory to spontaneous and induced EBV lytic activation, STAT3 functions via cellular PCBP2 to regulate lytic susceptibility, and suppression of PCBP2 levels is sufficient to increase the number of EBV lytic cells. We expect that these findings and the genome-wide resources that they provide will accelerate our understanding of a longstanding mystery in EBV biology and guide efforts to improve oncolytic therapy for EBV-associated cancers. Most humans are infected with Epstein-Barr virus (EBV), a cancer-causing virus. While EBV generally persists silently in B lymphocytes, periodic lytic (re)activation of latent virus is central to its life cycle and to most EBV-related diseases. However, a substantial fraction of EBV-infected B cells and tumor cells in a population is refractory to lytic activation. This resistance to lytic activation directly and profoundly impacts viral persistence and the effectiveness of oncolytic therapy for EBV(+) cancers. To identify the mechanisms that underlie susceptibility to EBV lytic activation, we used host gene and protein expression profiling of separated lytic and refractory cells. We find that STAT3, a transcription factor overactive in many cancers, regulates PCBP2, a protein important in RNA biogenesis, to regulate susceptibility to lytic cycle activation signals. These findings advance our understanding of EBV persistence and provide important leads on devising methods to improve viral oncolytic therapies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.

PubMed

Shiraki, Hiroaki; Kozar, Michael P; Melendez, Victor; Hudson, Thomas H; Ohrt, Colin; Magill, Alan J; Lin, Ai J

2011-01-13

In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivatives was prepared and assessed for antimalarial activities. The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 min, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth. The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone. Analogues with electron donating groups showed better activity than those with electron withdrawing substituents. Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC(50) data. The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests.

Correspondence of the brain's functional architecture during activation and rest

PubMed Central

Smith, Stephen M.; Fox, Peter T.; Miller, Karla L.; Glahn, David C.; Fox, P. Mickle; Mackay, Clare E.; Filippini, Nicola; Watkins, Kate E.; Toro, Roberto; Laird, Angela R.; Beckmann, Christian F.

2009-01-01

Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is “at rest.” In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically “active” even when at “rest.” PMID:19620724

Human T-cell leukemia virus type-1-encoded protein HBZ represses p53 function by inhibiting the acetyltransferase activity of p300/CBP and HBO1

PubMed Central

Hoang, Kimson; Ankney, John A.; Nguyen, Stephanie T.; Rushing, Amanda W.; Polakowski, Nicholas; Miotto, Benoit; Lemasson, Isabelle

2016-01-01

Adult T-cell leukemia (ATL) is an often fatal malignancy caused by infection with the complex retrovirus, human T-cell Leukemia Virus, type 1 (HTLV-1). In ATL patient samples, the tumor suppressor, p53, is infrequently mutated; however, it has been shown to be inactivated by the viral protein, Tax. Here, we show that another HTLV-1 protein, HBZ, represses p53 activity. In HCT116 p53+/+ cells treated with the DNA-damaging agent, etoposide, HBZ reduced p53-mediated activation of p21/CDKN1A and GADD45A expression, which was associated with a delay in G2 phase-arrest. These effects were attributed to direct inhibition of the histone acetyltransferase (HAT) activity of p300/CBP by HBZ, causing a reduction in p53 acetylation, which has be linked to decreased p53 activity. In addition, HBZ bound to, and inhibited the HAT activity of HBO1. Although HBO1 did not acetylate p53, it acted as a coactivator for p53 at the p21/CDKN1A promoter. Therefore, through interactions with two separate HAT proteins, HBZ impairs the ability of p53 to activate transcription. This mechanism may explain how p53 activity is restricted in ATL cells that do not express Tax due to modifications of the HTLV-1 provirus, which accounts for a majority of patient samples. PMID:26625199

Expression, purification, and kinetic characterization of full-length human fibroblast activation protein.

PubMed

Sun, Shaoxian; Albright, Charles F; Fish, Barbara H; George, Henry J; Selling, Bernard H; Hollis, Gregory F; Wynn, Richard

2002-03-01

Human fibroblast activation protein (FAP), an integral membrane serine protease, was produced in insect cells as a hexa-His-tagged protein using a recombinant baculovirus expression system. Two isoforms of FAP, glycosylated and nonglycosylated, were identified by Western blotting using an anti-His-tag antibody and separated by lectin chromatography. The glycosylated FAP was purified to near homogeneity using immobilized metal affinity chromatography and was shown to have both postprolyl dipeptidyl peptidase and postgelatinase activities. In contrast, the nonglycosylated isoform demonstrated no detectable gelatinase activity by either zymography or a fluorescence-based gelatinase activity assay. The kinetic parameters of the dipeptidyl peptidase activity for glycosylated FAP were determined using dipeptide Ala-Pro-7-amino-trifluoromethyl-coumarin as the substrate. The k(cat) is 2.0 s(-1) and k(cat)/K(m) is 1.0 x 10(4) M(-1) s(-1) at pH 8.5. The pH dependence of k(cat) reveals two ionization groups with pK(a1) of 7.0 and pK(a2) of 11.0. The pH profile of k(cat)/K(m) yields similar results with pK(a1) 6.2 and pK(a2) 11.0. The neutral pK(a1) is associated with His at the active site. The basic pK(a2) might be contributed from an ionization group that is not involved directly in catalysis, instead associated with the stability of the active site structure. Copyright 2002 Elsevier Science (USA).

Reminiscences of a journeyman scientist: studies of thermoregulation in non-human primates and humans.

PubMed

Adair, Eleanor Reed

2008-12-01

After graduating from Mount Holyoke College in 1948 where I majored in experimental psychology I worked at the College for 2 years with the Johns Hopkins Thermophysiological Unit. My graduate work later at the University of Wisconsin, centering on sensory psychology, culminated in my 1955 PhD thesis on human dark adaptation. I continued work in sensory psychology later with Neal Miller at Yale and then moved to the John B. Pierce Foundation--a Yale affiliate--where I began the studies of thermoregulation that constitute the center of my scientific career. Those studies were largely--later wholly--conducted using microwave energy as a thermal load and were thus published in Bioelectromagnetics even as I played an active role in the Bioelectromagnetics Society. In the beginning this work was centered on the responses of Squirrel Monkeys to thermal loads. Later, serving as Senior Scientist at the Air Force Research Laboratory at San Antonio, I completed an extensive analysis of thermal regulation in humans. I consider this work of special note inasmuch as the extraordinary human thermoregulatory ability was surely among the attributes that were paramount in initially separating humans from the other anthropoid primates.

Integrating the genomic architecture of human nucleolar organizer regions with the biophysical properties of nucleoli.

PubMed

Mangan, Hazel; Gailín, Michael Ó; McStay, Brian

2017-12-01

Nucleoli are the sites of ribosome biogenesis and the largest membraneless subnuclear structures. They are intimately linked with growth and proliferation control and function as sensors of cellular stress. Nucleoli form around arrays of ribosomal gene (rDNA) repeats also called nucleolar organizer regions (NORs). In humans, NORs are located on the short arms of all five human acrocentric chromosomes. Multiple NORs contribute to the formation of large heterochromatin-surrounded nucleoli observed in most human cells. Here we will review recent findings about their genomic architecture. The dynamic nature of nucleoli began to be appreciated with the advent of photodynamic experiments using fluorescent protein fusions. We review more recent data on nucleoli in Xenopus germinal vesicles (GVs) which has revealed a liquid droplet-like behavior that facilitates nucleolar fusion. Further analysis in both XenopusGVs and Drosophila embryos indicates that the internal organization of nucleoli is generated by a combination of liquid-liquid phase separation and active processes involving rDNA. We will attempt to integrate these recent findings with the genomic architecture of human NORs to advance our understanding of how nucleoli form and respond to stress in human cells. © 2017 Federation of European Biochemical Societies.

Metabolism of proposed nerve agent pretreatment, pyridostigmine bromide. Final report, December 1995-December 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leo, K.U.

A reverse phase High Pressure Liquid Chromatography (HPLC) method was developed to separate pyridostigmine bromide from four potential metabolites. Using male and female microsomes from both rat and human, our data suggest that pyridostigmine bromide is not metabolized by the human live microsomes or DNA expressed human CYP-450s via direct observation of no metabolites being formed for incubations up to 90 minutes. Indirect evidence that pyridostigmine metabolism is not via the major human hepatic CYP-450s involved in drug metabolism, 1A2, 2C9, 2E1, 2D6, and 3A4, was observed by failure to inhibit these isozymes while co-incubated with substrates specific for thosemore » isozymes at concentrations of 2-3 times Km. The following CYP-450 substrates were co-incubated with pyridostigmine: phenacetin, tolbutamide, chlorzoxazone, bufuralol, and testosterone. Using unlabelled and 14C-pyridostigmine, metabolite formation was not observed in both male and female rat and human subcellular fractions, specifically cytosol and S9, or under conditions favoring human FMO activity (pH 8.3). These findings indicate the metabolism of pyridostigmine bromide is unlikely to be under any component of sexual dimorphism.« less

Selective amplification of an mRNA and related pseudogene for a human ADP-ribosylation factor, a guanine nucleotide-dependent protein activator of cholera toxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monaco, L.; Murtagh, J.J.; Newman, K.B.

1990-03-01

ADP-ribosylation factors (ARFs) are {approx}20-kDa proteins that act as GTP-dependent allosteric activators of cholera toxin. With deoxyinosine-containing degenerate oligonucleotide primers corresponding to conserved GTP-binding domains in ARFs, the polymerase chain reaction (PCR) was used to amplify simultaneously from human DNA portions of three ARF genes that include codons for 102 amino acids, with intervening sequences. Amplification products that differed in size because of differences in intron sizes were separated by agarose gel electrophoresis. One amplified DNA contained no introns and had a sequence different from those of known AFRs. Based on this sequence, selective oligonucleotide probes were prepared and usedmore » to isolate clone {Psi}ARF 4, a putative ARF pseudogene, from a human genomic library in {lambda} phage EMBL3. Reverse transcription-PCR was then used to clone from human poly(A){sup +} RNA the cDNA corresponding to the expressed homolog of {Psi}ARF 4, referred to as human ARF 4. It appears that {Psi}ARF 4 arose during human evolution by integration of processed ARF 4 mRNA into the genome. Human ARF 4 differs from previously identified mammalian ARFs 1, 2, and 3. Hybridization of ARF 4-specific oligonucleotide probes with human, bovine, and rat RNA revealed a single 1.8-kilobase mRNA, which was clearly distinguished from the 1.9-kilobase mRNA for ARF 1 in these tissues. The PCR provides a powerful tool for investigating diversity in this and other multigene families, especially with primers targeted at domains believed to have functional significance.« less

Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells.

PubMed

Ramirez-Tagle, Rodrigo; Escobar, Carlos A; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

2016-02-22

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4'-trimethoxy-2'-hydroxy-chalcone (CH1) and 3'-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

Aliphatic alcohols in spirits inhibit phagocytosis by human monocytes.

PubMed

Pál, László; Árnyas, Ervin M; Bujdosó, Orsolya; Baranyi, Gergő; Rácz, Gábor; Ádány, Róza; McKee, Martin; Szűcs, Sándor

2015-04-01

A large volume of alcoholic beverages containing aliphatic alcohols is consumed worldwide. Previous studies have confirmed the presence of ethanol-induced immunosuppression in heavy drinkers, thereby increasing susceptibility to infectious diseases. However, the aliphatic alcohols contained in alcoholic beverages might also impair immune cell function, thereby contributing to a further decrease in microbicidal activity. Previous research has shown that aliphatic alcohols inhibit phagocytosis by granulocytes but their effect on human monocytes has not been studied. This is important as they play a crucial role in engulfment and killing of pathogenic microorganisms and a decrease in their phagocytic activity could lead to impaired antimicrobial defence in heavy drinkers. The aim of this study was to measure monocyte phagocytosis following their treatment with those aliphatic alcohols detected in alcoholic beverages. Monocytes were separated from human peripheral blood and phagocytosis of opsonized zymosan particles by monocytes treated with ethanol and aliphatic alcohols individually and in combination was determined. It was shown that these alcohols could suppress the phagocytic activity of monocytes in a concentration-dependent manner and when combined with ethanol, they caused a further decrease in phagocytosis. Due to their additive effects, it is possible that they may inhibit phagocytosis in a clinically meaningful way in alcoholics and episodic heavy drinkers thereby contribute to their increased susceptibility to infectious diseases. However, further research is needed to address this question.

DNase I hypersensitivity and epsilon-globin transcriptional enhancement are separable in locus control region (LCR) HS1 mutant human beta-globin YAC transgenic mice.

PubMed

Shimotsuma, Motoshi; Okamura, Eiichi; Matsuzaki, Hitomi; Fukamizu, Akiyoshi; Tanimoto, Keiji

2010-05-07

Expression of the five beta-like globin genes (epsilon, Ggamma, Agamma, delta, beta) in the human beta-globin locus depends on enhancement by the locus control region, which consists of five DNase I hypersensitive sites (5'HS1 through 5'HS5). We report here a novel enhancer activity in 5'HS1 that appears to be potent in transfected K562 cells. Deletion analyses identified a core activating element that bound to GATA-1, and a two-nucleotide mutation that disrupted GATA-1 binding in vitro abrogated 5'HS1 enhancer activity in transfection experiments. To determine the in vivo role of this GATA site, we generated multiple lines of human beta-globin YAC transgenic mice bearing the same two-nucleotide mutation. In the mutant mice, epsilon-, but not gamma-globin, gene expression in primitive erythroid cells was severely attenuated, while adult beta-globin gene expression in definitive erythroid cells was unaffected. Interestingly, DNaseI hypersensitivity near the 5'HS1 mutant sequence was eliminated in definitive erythroid cells, whereas it was only mildly affected in primitive erythroid cells. We therefore conclude that, although the GATA site in 5'HS1 is critical for efficient epsilon-globin gene expression, hypersensitive site formation per se is independent of 5'HS1 function, if any, in definitive erythroid cells.

Recognizing Age-Separated Face Images: Humans and Machines

PubMed Central

Yadav, Daksha; Singh, Richa; Vatsa, Mayank; Noore, Afzel

2014-01-01

Humans utilize facial appearance, gender, expression, aging pattern, and other ancillary information to recognize individuals. It is interesting to observe how humans perceive facial age. Analyzing these properties can help in understanding the phenomenon of facial aging and incorporating the findings can help in designing effective algorithms. Such a study has two components - facial age estimation and age-separated face recognition. Age estimation involves predicting the age of an individual given his/her facial image. On the other hand, age-separated face recognition consists of recognizing an individual given his/her age-separated images. In this research, we investigate which facial cues are utilized by humans for estimating the age of people belonging to various age groups along with analyzing the effect of one's gender, age, and ethnicity on age estimation skills. We also analyze how various facial regions such as binocular and mouth regions influence age estimation and recognition capabilities. Finally, we propose an age-invariant face recognition algorithm that incorporates the knowledge learned from these observations. Key observations of our research are: (1) the age group of newborns and toddlers is easiest to estimate, (2) gender and ethnicity do not affect the judgment of age group estimation, (3) face as a global feature, is essential to achieve good performance in age-separated face recognition, and (4) the proposed algorithm yields improved recognition performance compared to existing algorithms and also outperforms a commercial system in the young image as probe scenario. PMID:25474200

Recognizing age-separated face images: humans and machines.

PubMed

Yadav, Daksha; Singh, Richa; Vatsa, Mayank; Noore, Afzel

2014-01-01

Humans utilize facial appearance, gender, expression, aging pattern, and other ancillary information to recognize individuals. It is interesting to observe how humans perceive facial age. Analyzing these properties can help in understanding the phenomenon of facial aging and incorporating the findings can help in designing effective algorithms. Such a study has two components--facial age estimation and age-separated face recognition. Age estimation involves predicting the age of an individual given his/her facial image. On the other hand, age-separated face recognition consists of recognizing an individual given his/her age-separated images. In this research, we investigate which facial cues are utilized by humans for estimating the age of people belonging to various age groups along with analyzing the effect of one's gender, age, and ethnicity on age estimation skills. We also analyze how various facial regions such as binocular and mouth regions influence age estimation and recognition capabilities. Finally, we propose an age-invariant face recognition algorithm that incorporates the knowledge learned from these observations. Key observations of our research are: (1) the age group of newborns and toddlers is easiest to estimate, (2) gender and ethnicity do not affect the judgment of age group estimation, (3) face as a global feature, is essential to achieve good performance in age-separated face recognition, and (4) the proposed algorithm yields improved recognition performance compared to existing algorithms and also outperforms a commercial system in the young image as probe scenario.

Portable vibration-assisted filtration device for on-site isolation of blood cells or pathogenic bacteria from whole human blood.

PubMed

Kim, Yong Tae; Park, Kyun Joo; Kim, Seyl; Kim, Soon Ae; Lee, Seok Jae; Kim, Do Hyun; Lee, Tae Jae; Lee, Kyoung G

2018-03-01

Isolation of specific cells from whole blood is important to monitor disease prognosis and diagnosis. In this study, a vibration-assisted filtration (VF) device has been developed for isolation and recovery of specific cells such as leukocytes and pathogenic bacteria from human whole blood. The VF device is composed of three layers which was fabricated using injection molding with cyclic olefin copolymer (COC) pellets consisting of: a top layer with coin-type vibration motor (Ф = 10mm), a middle plate with a 1μm or 3μm-pore filter membrane to separate of Staphylococcus aureus (S. aureus) cells or leukocytes (i.e. white blood cells) respectively, and a bottom chamber with conical-shaped microstructure. One milliliter of human whole blood was injected into a sample loading chamber using a 3μm-pore filter equipped in the VF device and the coin-type vibration motor applied external vibration force by generating a rotational fluid which enhances the filtration velocity due to the prevention of the cell clogging on the filter membrane. The effluent blood such as erythrocytes, platelet, and plasma was collected at the bottom chamber while the leukocytes were sieved by the filter membrane. The vibration-assisted leukocyte separation was able to finish within 200s while leukocyte separation took 1200s without vibration. Moreover, we successfully separated S. aureus from human whole blood using a 1μm-pore filter equipped VF device and it was further confirmed by genetic analysis. The proposed VF device provides an advanced cell separation platform in terms of simplicity, fast separation, and portability in the fields of point-of-care diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

Innate lymphoid cells in autoimmunity and chronic inflammatory diseases.

PubMed

Xiong, Tingting; Turner, Jan-Eric

2018-03-22

Abnormal activation of the innate immune system is a common feature of autoimmune and chronic inflammatory diseases. Since their identification as a separate family of leukocytes, innate lymphoid cells (ILCs) have emerged as important effector cells of the innate immune system. Alterations in ILC function and subtype distribution have been observed in a variety of immune-mediated diseases in humans and evidence from experimental models suggests a subtype specific role of ILCs in the pathophysiology of autoimmune inflammation. In this review, we discuss recent advances in the understanding of ILC biology in autoimmune and chronic inflammatory disorders, including multiple sclerosis, inflammatory bowel diseases, psoriasis, and rheumatic diseases, with a special focus on the potential of ILCs as therapeutic targets for the development of novel treatment strategies in humans.

Quantification of Dihydroxyacetone Phosphate (DHAP) in Human Red Blood Cells by HPLC-TripleTOF 5600™ Mass Spectrometer.

PubMed

Deng, Shuang; Scott, David; Myers, Douglas; Garg, Uttam

2016-01-01

Triosephosphate isomerase (TPI) is a glycolytic enzyme which catalyzes the interconversion between glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP). TPI deficiency results in accumulation of DHAP in human red blood cells and other tissues. The disease is characterized by congenital hemolytic anemia, and progressive neuromuscular dysfunction. The laboratory diagnosis is generally made by measurement of TPI activity in RBCs. Measurement of DHAP can be useful in further confirmation and follow-up of the disease. We developed HPLC/TOF-MS method for quantitation of DHAP in RBCs. The method involves simple protein precipitation, reverse phase C8 column chromatography, ion pairing with tributylamine, and long run time of 50 min to separate the two isomers (G3P and DHAP).

Separation of Albumin, Ceruloplasmin, and Transferrin from Human Plasma.

ERIC Educational Resources Information Center

Barnes, Grady; Frieden, Earl

1982-01-01

Procedures are provided for separating the principal metalloproteins (albumin, ceruloplasmin, and transferrin) from plasma using column chromatographic techniques. The experiment can be completed in two separate three-hour laboratory periods during which column chromatography is illustrated and the effect of pH on charge and affinity of a protein…

45 CFR 302.12 - Single and separate organizational unit.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 2 2011-10-01 2011-10-01 false Single and separate organizational unit. 302.12... (CHILD SUPPORT ENFORCEMENT PROGRAM), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES STATE PLAN REQUIREMENTS § 302.12 Single and separate organizational unit. (a) The State...

21 CFR 864.8500 - Lymphocyte separation medium.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

21 CFR 864.8500 - Lymphocyte separation medium.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

21 CFR 864.8500 - Lymphocyte separation medium.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

21 CFR 864.8500 - Lymphocyte separation medium.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

21 CFR 864.8500 - Lymphocyte separation medium.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

Limb suction evoked during arterial occlusion causes systemic sympathetic activity in humans

PubMed Central

Cui, Jian; Blaha, Cheryl; Herr, Michael D.; Drew, Rachel C.; Muller, Matthew D.

2015-01-01

Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP). We hypothesized that the application of suction to the human limbs would activate this venous distension reflex and raise sympathetic outflow. We placed airtight pressure tanks and applied 100 mmHg negative pressure to an arterially occluded limb (occlusion and suction, O&S) to induce tissue deformation without fluid translocation. BP, heart rate (HR), and MSNA were assessed in 19 healthy subjects during 2 min of arm or leg O&S. Occlusion without suction served as a control. During a separate visit, saline (5% forearm volume) was infused into veins of the arterially occluded arm (n = 13). The O&S increased limb circumference, MSNA burst rate (arm: Δ6.7 ± 0.7; leg: Δ6.8 ± 0.7 bursts/min), and total activity (arm: Δ199 ± 14; leg: Δ172 ± 22 units/min) and BP (arm: Δ4.3 ± 0.3; leg: Δ9.4 ± 1.4 mmHg) from the baseline. The MSNA and BP responses during arm O&S correlated with those during leg O&S. Occlusion alone had no effect on MSNA and BP. MSNA (r = 0.607) responses during arm O&S correlated with those evoked by the saline infusion into the arm. These correlations suggest that sympathetic activation during limb O&S is likely, at least partially, to be evoked via the venous distension reflex. These data suggest that suction of an occluded limb evokes sympathetic activation and that the limb venous distension reflex exists in arms and legs of normal humans. PMID:26136530

Antiproliferative and apoptotic activities of extracts of Asclepias subulata.

PubMed

Rascón Valenzuela, Luisa Alondra; Jiménez Estrada, Manuel; Velázquez Contreras, Carlos Arturo; Garibay Escobar, Adriana; Medina Juárez, Luis Angel; Gámez Meza, Nohemi; Robles Zepeda, Ramón Enrique

2015-01-01

Asclepias subulata Decne. (Apocynaceae) is a shrub used in the Mexican traditional medicine for the treatment of cancer. The objective of this study was to evaluate the antiproliferative activity of methanol extract of aerial parts of A. subulata and its fractions against different cancer cell lines. Additionally, we analyzed the mechanism of action of the active fractions. Methanol extract fractions were prepared by serial extraction with n-hexane, ethyl acetate, and ethanol. The antiproliferative activity of methanol extract and its fractions was evaluated, against several murine (M12.C3.F6, RAW 264.7, and L929) and human (HeLa, A549, PC-3, LS 180, and ARPE-19) cell lines by the MTT assay, using concentrations of 0.4-400 µg/mL for 48 h. Ethanol and residual fractions were separated using silica gel column. Apoptosis induction of cancer cells was evaluated by Annexin and JC-1 staining using flow cytometry. Methanol extract and its fractions showed antiproliferative activity against all human cancer cell lines tested. Methanol extract had the highest antiproliferative activity on A549 and HeLa cells (IC50 values < 0.4 and 8.7 µg/mL, respectively). Ethanol and residual fractions exerted significant antiproliferative effect on A549 (IC50 < 0.4 µg/mL) and PC3 cells (IC50 1.4 and 5.1 µg/mL). Apoptotic assays showed that CEF7, CEF9, CRF6, and CRF5 fractions induced mitochondrial depolarization in A549 cells, 70, 73, 77, and 80%, respectively. Those fractions triggered the apoptosis mitochondrial pathway. Our data show that A. subulata extracts have potent antiproliferative properties on human cancer cell lines. This plant should be considered an important source of potent anticancer compounds.

Assessing Brain–Muscle Connectivity in Human Locomotion through Mobile Brain/Body Imaging: Opportunities, Pitfalls, and Future Directions

PubMed Central

Gennaro, Federico; de Bruin, Eling D.

2018-01-01

Assessment of the cortical role during bipedalism has been a methodological challenge. While surface electroencephalography (EEG) is capable of non-invasively measuring cortical activity during human locomotion, it is associated with movement artifacts obscuring cerebral sources of activity. Recently, statistical methods based on blind source separation revealed potential for resolving this issue, by segregating non-cerebral/artifactual from cerebral sources of activity. This step marked a new opportunity for the investigation of the brains’ role while moving and was tagged mobile brain/body imaging (MoBI). This methodology involves simultaneous mobile recording of brain activity with several other body behavioral variables (e.g., muscle activity and kinematics), through wireless recording wearable devices/sensors. Notably, several MoBI studies using EEG–EMG approaches recently showed that the brain is functionally connected to the muscles and active throughout the whole gait cycle and, thus, rejecting the long-lasting idea of a solely spinal-driven bipedalism. However, MoBI and brain/muscle connectivity assessments during human locomotion are still in their fledgling state of investigation. Mobile brain/body imaging approaches hint toward promising opportunities; however, there are some remaining pitfalls that need to be resolved before considering their routine clinical use. This article discusses several of these pitfalls and proposes research to address them. Examples relate to the validity, reliability, and reproducibility of this method in ecologically valid scenarios and in different populations. Furthermore, whether brain/muscle connectivity within the MoBI framework represents a potential biomarker in neuromuscular syndromes where gait disturbances are evident (e.g., age-related sarcopenia) remains to be determined. PMID:29535995

Chemical nature and immunotoxicological properties of arachidonic acid degradation products formed by exposure to ozone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madden, M.C.; Friedman, M.; Hanley, N.

1993-06-01

Ozone (O3) exposure in vivo has been reported to degrade arachidonic acid (AA) in the lungs of rodents. The O3-degraded AA products may play a role in the responses to this toxicant. To study the chemical nature and biological activity of O3-exposed AA, we exposed AA in a cell-free, aqueous environment to air, 0.1 ppm O3, or 1.0 ppm O3 for 30-120 min. AA exposed to air was not degraded. All O3 exposures degraded > 98% of the AA to more polar products, which were predominantly aldehydic substances (as determined by reactivity with 2,4-dinitrophenylhydrazine and subsequent separation by HPLC) andmore » hydrogen peroxide. The type and amount of aldehydic substances formed depended on the O3 concentration and exposure duration. A human bronchial epithelial cell line (BEAS-2B, S6 subclone) exposed in vitro to either 0.1 ppm or 1.0 ppm O3 for 1 hr produced AA-derived aldehydic substances, some of which eluted with similar retention times as the aldehydic substances derived from O3 degradation of AA in the cell-free system. In vitro, O3-degraded AA induced an increase in human peripheral blood polymorphonuclear leukocyte (PMN) polarization, decreased human peripheral blood T-lymphocyte proliferation in response to mitogens, and decreased human peripheral blood natural killer cell lysis of K562 target cells. The aldehydic substances, but not hydrogen peroxide, appeared to be the principal active agents responsible for the observed effects. O3-degraded AA may play a role in the PMN influx into lungs and in decreased T-lymphocyte mitogenesis and natural killer cell activity observed in humans and rodents exposed to O3.« less

Learning and Recognition of a Non-conscious Sequence of Events in Human Primary Visual Cortex.

PubMed

Rosenthal, Clive R; Andrews, Samantha K; Antoniades, Chrystalina A; Kennard, Christopher; Soto, David

2016-03-21

Human primary visual cortex (V1) has long been associated with learning simple low-level visual discriminations [1] and is classically considered outside of neural systems that support high-level cognitive behavior in contexts that differ from the original conditions of learning, such as recognition memory [2, 3]. Here, we used a novel fMRI-based dichoptic masking protocol-designed to induce activity in V1, without modulation from visual awareness-to test whether human V1 is implicated in human observers rapidly learning and then later (15-20 min) recognizing a non-conscious and complex (second-order) visuospatial sequence. Learning was associated with a change in V1 activity, as part of a temporo-occipital and basal ganglia network, which is at variance with the cortico-cerebellar network identified in prior studies of "implicit" sequence learning that involved motor responses and visible stimuli (e.g., [4]). Recognition memory was associated with V1 activity, as part of a temporo-occipital network involving the hippocampus, under conditions that were not imputable to mechanisms associated with conscious retrieval. Notably, the V1 responses during learning and recognition separately predicted non-conscious recognition memory, and functional coupling between V1 and the hippocampus was enhanced for old retrieval cues. The results provide a basis for novel hypotheses about the signals that can drive recognition memory, because these data (1) identify human V1 with a memory network that can code complex associative serial visuospatial information and support later non-conscious recognition memory-guided behavior (cf. [5]) and (2) align with mouse models of experience-dependent V1 plasticity in learning and memory [6]. Copyright © 2016 Elsevier Ltd. All rights reserved.

Secreted histidyl-tRNA synthetase splice variants elaborate major epitopes for autoantibodies in inflammatory myositis.

PubMed

Zhou, Jie J; Wang, Feng; Xu, Zhiwen; Lo, Wing-Sze; Lau, Ching-Fun; Chiang, Kyle P; Nangle, Leslie A; Ashlock, Melissa A; Mendlein, John D; Yang, Xiang-Lei; Zhang, Mingjie; Schimmel, Paul

2014-07-11

Inflammatory and debilitating myositis and interstitial lung disease are commonly associated with autoantibodies (anti-Jo-1 antibodies) to cytoplasmic histidyl-tRNA synthetase (HisRS). Anti-Jo-1 antibodies from different disease-afflicted patients react mostly with spatially separated epitopes in the three-dimensional structure of human HisRS. We noted that two HisRS splice variants (SVs) include these spatially separated regions, but each SV lacks the HisRS catalytic domain. Despite the large deletions, the two SVs cross-react with a substantial population of anti-Jo-l antibodies from myositis patients. Moreover, expression of at least one of the SVs is up-regulated in dermatomyositis patients, and cell-based experiments show that both SVs and HisRS can be secreted. We suggest that, in patients with inflammatory myositis, anti-Jo-1 antibodies may have extracellular activity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Multidimensional bioseparation with modular microfluidics

DOEpatents

Chirica, Gabriela S.; Renzi, Ronald F.

2013-08-27

A multidimensional chemical separation and analysis system is described including a prototyping platform and modular microfluidic components capable of rapid and convenient assembly, alteration and disassembly of numerous candidate separation systems. Partial or total computer control of the separation system is possible. Single or multiple alternative processing trains can be tested, optimized and/or run in parallel. Examples related to the separation and analysis of human bodily fluids are given.

Quantitative analysis of impact of awareness-raising activities on organic solid waste separation behaviour in Balikpapan City, Indonesia.

PubMed

Murase, Noriaki; Murayama, Takehiko; Nishikizawa, Shigeo; Sato, Yuriko

2017-10-01

Many cities in Indonesia are under pressure to reduce solid waste and dispose of it properly. In response to this pressure, the Japan International Cooperation Agency and the Indonesian Government have implemented a solid waste separation and collection project to reduce solid waste in the target area (810 households) of Balikpapan City. We used a cluster randomised controlled trial method to measure the impact of awareness-raising activities that were introduced by the project on residents' organic solid waste separation behaviour. The level of properly separated organic solid waste increased by 6.0% in areas that conducted awareness-raising activities. Meanwhile, the level decreased by 3.6% in areas that did not conduct similar activities. Therefore, in relative comparison, awareness-raising increased the level by 9.6%. A comparison among small communities in the target area confirmed that awareness-raising activities had a significant impact on organic solid waste separation. High frequencies of monitoring at waste stations and door-to-door visits by community members had a positive impact on organic solid waste separation. A correlation between the proximity of environmental volunteers' houses to waste stations and a high level of separation was also confirmed. The awareness-raising activities introduced by the project led to a significant increase in the separation of organic solid waste.

Phase Separation in Solutions of Monoclonal Antibodies

NASA Astrophysics Data System (ADS)

Benedek, George; Wang, Ying; Lomakin, Aleksey; Latypov, Ramil

2012-02-01

We report the observation of liquid-liquid phase separation (LLPS) in a solution of humanized monoclonal antibodies, IgG2, and the effects of human serum albumin, a major blood protein, on this phase separation. We find a significant reduction of phase separation temperature in the presence of albumin, and a preferential partitioning of the albumin into the antibody-rich phase. We provide a general thermodynamic analysis of the antibody-albumin mixture phase diagram and relate its features to the magnitude of the effective inter-protein interactions. Our analysis suggests that additives (HSA in this report), which have moderate attraction with antibody molecules, may be used to forestall undesirable protein condensation in antibody solutions. Our findings are relevant to understanding the stability of pharmaceutical solutions of antibodies and the mechanisms of cryoglobulinemia.

Effects of maternal separation, early handling, and gonadal sex on regional metabolic capacity of the preweanling rat brain

PubMed Central

Spivey, Jaclyn M.; Padilla, Eimeira; Shumake, Jason D.; Gonzalez-Lima, F.

2010-01-01

This is the first study to assess the effects of mother-infant separation on regional metabolic capacity in the preweanling rat brain. Mother-infant separation is generally known to be stressful for rat pups. Holtzman adolescent rats show a depressive-like behavioral phenotype after maternal separation during the preweanling period. However, information is lacking on the effects of maternal separation on the brains of rat pups. We addressed this issue by mapping the brains of preweanling Holtzman rat pups using cytochrome oxidase histochemistry, which reflects long-term changes in brain metabolic capacity, following two weeks of repeated, prolonged maternal separation, and compared this to both early handled and non-handled pups. Quantitative image analysis revealed that maternal separation reduced cytochrome oxidase activity in the medial prefrontal cortex and nucleus accumbens shell. Maternal separation reduced prefrontal cytochrome oxidase to a greater degree in female pups than in males. Early handling reduced cytochrome oxidase activity in the posterior parietal cortex, ventral tegmental area, and subiculum, but increased cytochrome oxidase activity in the lateral frontal cortex. The sex-dependent effects of early handling on cytochrome oxidase activity were limited to the medial prefrontal cortex. Regardless of separation group, females had greater cytochrome oxidase activity in the habenula and ventral tegmental area compared to males. These findings suggest that early life mother-infant separation results in dysfunction of prefrontal and mesolimbic regions in the preweanling rat brain that may contribute to behavioral changes later in life. PMID:20969837

A peristaltic pump driven 89Zr separation module

NASA Astrophysics Data System (ADS)

Siikanen, J.; Peterson, M.; Tran, T. A.; Roos, P.; Ohlsson, T.; Sandell, A.

2012-12-01

To facilitate the separation of 89Zr produced in yttrium foils, an automated separation module was designed and assembled. The module separates more than 85% of produced 89Zr - activity in 3 g foils in less than 90 min. About 10 % remains in the dissolving vial. The quality of the separated 89Zr activity was investigated for labeling of the HER2-binding monoclonal antibody fragment, trastuzumab-Fab.

Creating Concepts from Converging Features in Human Cortex

PubMed Central

Coutanche, Marc N.; Thompson-Schill, Sharon L.

2015-01-01

To make sense of the world around us, our brain must remember the overlapping features of millions of objects. Crucially, it must also represent each object's unique feature-convergence. Some theories propose that an integration area (or “convergence zone”) binds together separate features. We report an investigation of our knowledge of objects' features and identity, and the link between them. We used functional magnetic resonance imaging to record neural activity, as humans attempted to detect a cued fruit or vegetable in visual noise. Crucially, we analyzed brain activity before a fruit or vegetable was present, allowing us to interrogate top-down activity. We found that pattern-classification algorithms could be used to decode the detection target's identity in the left anterior temporal lobe (ATL), its shape in lateral occipital cortex, and its color in right V4. A novel decoding-dependency analysis revealed that identity information in left ATL was specifically predicted by the temporal convergence of shape and color codes in early visual regions. People with stronger feature-and-identity dependencies had more similar top-down and bottom-up activity patterns. These results fulfill three key requirements for a neural convergence zone: a convergence result (object identity), ingredients (color and shape), and the link between them. PMID:24692512

Purification and some properties of the protein component of tissue thromboplastin from human brain.

PubMed Central

Bjorklid, E; Storm, E

1977-01-01

The protein component of tissue thromboplastib (Factor III) from human brain was purified by extraction of a microsomal fraction with sodium deoxycholate, gel filtration of the extract on Sephadex G-100 and preparative polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. The product, apoprotein III, was homogeneous by anayltical polyacrylamide-gel electrophoresis, and it induced monospecific antibodies in rabbits and goat as shown by immunodiffusion and immunoelectrophoresis. Amino acid- and carbohydrate-analysis data for apoprotein III are presented. The carbohydrate moiety of the protein consists of fucose, mannose, galactose, N-acetylglucosamine and N-acetylneuraminate, amounting to a total content of 6.3g/100g. The apoprotein alone had no procoagulant activity. When Factor III was reconstituted by combining the pure apoprotein with a purified lipid fraction from the deoxycholate extract of crude Factor III, a high and optimal procoagulant activity was obtained at a phospholipid/protein ratio of 1.1g/g. Phosphatidylethanolamine alone had a weak but significant ability to restore activity, whereas phosphatidylcholine and phosphatidylserine separately had almost none. Two-component mixtures were on average more effective, and three-component mixtures far more effective, than the single phospholipids. The inclusion of a small amount of phosphatidylserine was very important for high activity. Images Fig. 2. PLATE 1 PMID:889578

Simplified Large-Scale Refolding, Purification, and Characterization of Recombinant Human Granulocyte-Colony Stimulating Factor in Escherichia coli

PubMed Central

Kim, Chang Kyu; Lee, Chi Ho; Lee, Seung-Bae; Oh, Jae-Wook

2013-01-01

Granulocyte-colony stimulating factor (G-CSF) is a pleiotropic cytokine that stimulates the development of committed hematopoietic progenitor cells and enhances the functional activity of mature cells. Here, we report a simplified method for fed-batch culture as well as the purification of recombinant human (rh) G-CSF. The new system for rhG-CSF purification was performed using not only temperature shift strategy without isopropyl-l-thio-β-d-galactoside (IPTG) induction but also the purification method by a single step of prep-HPLC after the pH precipitation of the refolded samples. Through these processes, the final cell density and overall yield of homogenous rhG-CSF were obtained 42.8 g as dry cell weights, 1.75 g as purified active proteins, from 1 L culture broth, respectively. The purity of rhG-CSF was finally 99% since the isoforms of rhG-CSF could be separated through the prep-HPLC step. The result of biological activity indicated that purified rhG-CSF has a similar profile to the World Health Organization (WHO) 2nd International Standard for G-CSF. Taken together, our results demonstrate that the simple purification through a single step of prep-HPLC may be valuable for the industrial-scale production of biologically active proteins. PMID:24224041

Capacity of tumor necrosis factor to augment lymphocyte-mediated tumor cell lysis of malignant mesothelioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowman, R.V.; Manning, L.S.; Davis, M.R.

1991-01-01

Recombinant human tumor necrosis factor (rHuTNF) was evaluated both for direct anti-tumor action against human malignant mesothelioma and for its capacity to augment the generation and lytic phases of lymphocyte-mediated cytotoxicity against this tumor. rHuTNF was directly toxic by MTT assay to one of two mesothelioma cell lines evaluated, but had no effect on susceptibility to subsequent lymphocyte-mediated lysis of either line. TNF alone was incapable of generating anti-mesothelioma lymphokine-activated killer cell (LAK) activity. Furthermore, it did not augment the degree or LAK activity produced by submaximal interleukin-2 (IL-2) concentrations nor did it augment lysis of mesothelioma cells by naturalmore » killer (NK) or LAK effector cells during the 4-hr 51chromium release cytolytic reaction. The studies also suggest that mesothelioma targets are less responsive to TNF plus submaximal IL-2 concentrations than the standard LAK sensitive target Daudi, raising the possibility that intermediate LAK sensitive tumors such as mesothelioma may require separate and specific evaluation in immunomodulation studies. This in vitro study indicates that use of low-dose rHuTNF and IL-2 is unlikely to be an effective substitute for high-dose IL-2 in generation and maintenance of LAK activity in adoptive immunotherapy for mesothelioma.« less

Electromyographic reflexes evoked in human flexor carpi radialis by tendon vibration.

PubMed

Cody, F W; Goodwin, C N; Richardson, H C

1990-10-01

The rectified, electromyographic (EMG) reflexes evoked in the voluntarily contracting flexor carpi radialis (FCR) muscle by vibration of its tendon were studied in healthy human subjects. Responses comprised a prominent, transient, short-latency (SL, 20-25 ms) increase in EMG, attributed to Ia mono- and/or oligo-synaptic action, followed by a series of less pronounced troughs and peaks of activity. Evidence of continuing Ia mono- or oligo-synaptic action was indicated by (i) the presence of small subpeaks, at vibration frequency, superimposed upon the excitatory components and (ii) the occurrence of a separate reduction in EMG, of consistent latency (ca. 30 ms), after cessation of stimulation. Progressively shortening the train of vibration from 29 cycles (at 145 Hz) to a single cycle significantly reduced net, excitatory reflex activity. Gradually increasing the level (10-50% maximum) of pre-existing voluntary contraction on top of which reflexes were elicited, by moderately prolonged (29 cycles) trains of vibration, resulted in small increases, in absolute terms, in SL peaks and in later, excitatory EMG activity. Excitatory reflexes, when normalised for pre-stimulus EMG, however, declined in an approximately hyperbolic manner with increasing background activity over this range. Thus, effective "automatic gain compensation" does not operate for vibration reflexes in FCR.

Simultaneous determination of sibutramine and its active metabolites in human plasma by LC-MS/MS and its application to a pharmacokinetic study.

PubMed

Bae, Jung-Woo; Choi, Chang-Ik; Jang, Choon-Gon; Lee, Seok-Yong

2011-11-01

A simple and sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) technique was developed and validated for the determination of sibutramine and its N-desmethyl metabolites (M1 and M2) in human plasma. After extraction with methyl t-butyl ether, chromatographic separation of analytes in human plasma was performed using a reverse-phase Luna C18 column with a mobile phase of acetonitrile-10 mm ammonium formate buffer (50:50, v/v) and quantified by ESI-MS/MS detection in positive ion mode. The flow rate of the mobile phase was 200 μL/min and the retention times of sibutramine, M1, M2 and internal standard (chlorpheniramine) were 1.5, 1.4, 1.3 and 0.9 min, respectively. The calibration curves were linear over the range 0.05-20 ng/mL, for sibutramine, M1 and M2. The lower limit of quantification was 0.05 ng/mL using 500 μL of human plasma. The mean accuracy and the precision in the intra- and inter-day validation for sibutramine, M1 and M2 were acceptable. This LC-MS/MS method showed improved sensitivity and a short run time for the quantification of sibutramine and its two active metabolites in plasma. The validated method was successfully applied to a pharmacokinetic study in human. Copyright © 2011 John Wiley & Sons, Ltd.

Growing children's bodies and minds: maximizing child nutrition and development.

PubMed

Engle, Patrice; Huffman, Sandra L

2010-06-01

For their optimal growth, and for greater long-term human capital development, children profit not only from improved nutrition but also from improved learning opportunities in the earliest years of life. This paper describes how actions to enhance optimal infant and young child nutrition can be linked with child development interventions for children under 3 years of age. In countries with high rates of malnutrition, linking these two components will result in synergies of program activities, and will bring about a greater impact at reduced cost than either activity conducted separately. New understanding of social marketing and communication strategies can increase effectiveness of linked interventions. Public-private partnerships to improve both child development and nutrition offer promise for sustainable interventions.

Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems.

PubMed

Castillo, Tiffany N; Pouliot, Michael A; Kim, Hyeon Joo; Dragoo, Jason L

2011-02-01

Clinical studies claim that platelet-rich plasma (PRP) shortens recovery times because of its high concentration of growth factors that may enhance the tissue repair process. Most of these studies obtained PRP using different separation systems, and few analyzed the content of the PRP used as treatment. This study characterized the composition of single-donor PRP produced by 3 commercially available PRP separation systems. Controlled laboratory study. Five healthy humans donated 100 mL of blood, which was processed to produce PRP using 3 PRP concentration systems (MTF Cascade, Arteriocyte Magellan, Biomet GPS III). Platelet, white blood cell (WBC), red blood cell, and fibrinogen concentrations were analyzed by automated systems in a clinical laboratory, whereas ELISA determined the concentrations of platelet-derived growth factor αβ and ββ (PDGF-αβ, PDGF-ββ), transforming growth factor β1 (TGF-β1), and vascular endothelial growth factor (VEGF). There was no significant difference in mean PRP platelet, red blood cell, active TGF-β1, or fibrinogen concentrations among PRP separation systems. There was a significant difference in platelet capture efficiency. The highest platelet capture efficiency was obtained with Cascade, which was comparable with Magellan but significantly higher than GPS III. There was a significant difference among all systems in the concentrations of WBC, PDGF-αβ, PDGF-ββ, and VEGF. The Cascade system concentrated leukocyte-poor PRP, compared with leukocyte-rich PRP from the GPS III and Magellan systems. The GPS III and Magellan concentrate leukocyte-rich PRP, which results in increased concentrations of WBCs, PDGF-αβ, PDGF-ββ, and VEGF as compared with the leukocyte-poor PRP from Cascade. Overall, there was no significant difference among systems in the platelet concentration, red blood cell, active TGF-β1, or fibrinogen levels. Products from commercially available PRP separation systems produce differing concentrations of growth factors and WBCs. Further research is necessary to determine the clinical relevance of these findings.

Surface charge dependent separation of modified and hybrid ferritin in native PAGE: Impact of lysine 104.

PubMed

Subhadarshanee, Biswamaitree; Mohanty, Abhinav; Jagdev, Manas Kumar; Vasudevan, Dileep; Behera, Rabindra K

2017-10-01

Preparation of modified and hybrid ferritin provides a great opportunity to understand the mechanisms of iron loading/unloading, protein self-assembly, size constrained nanomaterial synthesis and targeted drug delivery. However, the large size (M.W.=490kDa) has been limiting the separation of different modified and/or hybrid ferritin nanocages from each other in their intact assembled form and further characterization. Native polyacrylamide gel electrophoresis (PAGE) separates proteins on the basis of both charge and mass, while maintaining their overall native structure and activity. Altering surface charge distribution by substitution of amino acid residues located at the external surface of ferritin (K104E & D40A) affected the migration rate in native PAGE while internal modification had little effect. Crystal structures confirmed that ferritin nanocages made up of subunits with single amino acid substitutions retain the overall structure of ferritin nanocage. Taking advantage of K104E migration behavior, formation of hybrid ferritins with subunits of wild type (WT) and K104E were confirmed and separated in native PAGE. Cage integrity and iron loading ability (ferritin activity) were also tested. The migration pattern of hybrid ferritins in native PAGE depends on the subunit ratio (WT: K104E) in the ferritin cage. Our work shows that native PAGE can be exploited in nanobiotechnology, by analyzing modifications of large proteins like ferritin. Native PAGE, a simple, straight-forward technique, can be used to analyze small modification (by altering external surface charge) in large proteins like ferritin, without disintegrating its self-assembled nanocage structure. In doing so, native PAGE can complement the information obtained from mass spectrometry. The confirmation and separation of modified and hybrid ferritin protein nanocages in native PAGE, opens up various prospects of bio-conjugation, which can be useful in targeted drug delivery, nanobiotechnology and in understanding nature's idea of synthesizing hybrid ferritins in different human tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

Human Hippocampal Dynamics during Response Conflict.

PubMed

Oehrn, Carina R; Baumann, Conrad; Fell, Juergen; Lee, Hweeling; Kessler, Henrik; Habel, Ute; Hanslmayr, Simon; Axmacher, Nikolai

2015-08-31

Besides its relevance for declarative memory functions, hippocampal activation has been observed during disambiguation of uncertainty and conflict. Uncertainty and conflict may arise on various levels. On the perceptual level, the hippocampus has been associated with signaling of contextual deviance and disambiguation of similar items (i.e., pattern separation). Furthermore, conflicts can occur on the response level. Animal experiments showed a role of the hippocampus for inhibition of prevailing response tendencies and suppression of automatic stimulus-response mappings, potentially related to increased theta oscillations (3-8 Hz). In humans, a recent fMRI study demonstrated hippocampal involvement in approach-avoidance conflicts. However, the more general significance of hippocampal activity for dealing with response conflicts also on a cognitive level is still unknown. Here, we investigated the role of the hippocampus for response conflict in the Stroop task by combining intracranial electroencephalography (iEEG) recordings from the hippocampus of epilepsy patients with region of interest-based fMRI in healthy participants. Both methods revealed converging evidence that the hippocampus is recruited in a regionally specific manner during response conflict. Moreover, our iEEG data show that this activation depends on theta oscillations and is relevant for successful response conflict resolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

Residual effects of cannabis use in adolescent and adult brains - A meta-analysis of fMRI studies.

PubMed

Blest-Hopley, Grace; Giampietro, Vincent; Bhattacharyya, Sagnik

2018-05-01

While numerous studies have investigated the residual effects of cannabis use on human brain function, results of these studies have been inconsistent. Using meta-analytic approaches we summarize the effects of prolonged cannabis exposure on human brain function as measured using task-based functional MRI (fMRI) across studies employing a range of cognitive activation tasks comparing regular cannabis users with non-users. Separate meta-analyses were carried out for studies investigating adult and adolescent cannabis users. Systematic literature search identified 20 manuscripts (13 adult and 7 adolescent studies) meeting study inclusion criteria. Adult analyses compared 530 cannabis users to 580 healthy controls while adolescent analyses compared 219 cannabis users to 224 healthy controls. In adult cannabis users brain activation was increased in the superior and posterior transverse temporal and inferior frontal gyri and decreased in the striate area, insula and middle temporal gyrus. In adolescent cannabis users, activation was increased in the inferior parietal gyrus and putamen compared to healthy controls. Functional alteration in these areas may reflect compensatory neuroadaptive changes in cannabis users. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neurochemical responses to chromatic and achromatic stimuli in the human visual cortex.

PubMed

Bednařík, Petr; Tkáč, Ivan; Giove, Federico; Eberly, Lynn E; Deelchand, Dinesh K; Barreto, Felipe R; Mangia, Silvia

2018-02-01

In the present study, we aimed at determining the metabolic responses of the human visual cortex during the presentation of chromatic and achromatic stimuli, known to preferentially activate two separate clusters of neuronal populations (called "blobs" and "interblobs") with distinct sensitivity to color or luminance features. Since blobs and interblobs have different cytochrome-oxidase (COX) content and micro-vascularization level (i.e., different capacities for glucose oxidation), different functional metabolic responses during chromatic vs. achromatic stimuli may be expected. The stimuli were optimized to evoke a similar load of neuronal activation as measured by the bold oxygenation level dependent (BOLD) contrast. Metabolic responses were assessed using functional 1 H MRS at 7 T in 12 subjects. During both chromatic and achromatic stimuli, we observed the typical increases in glutamate and lactate concentration, and decreases in aspartate and glucose concentration, that are indicative of increased glucose oxidation. However, within the detection sensitivity limits, we did not observe any difference between metabolic responses elicited by chromatic and achromatic stimuli. We conclude that the higher energy demands of activated blobs and interblobs are supported by similar increases in oxidative metabolism despite the different capacities of these neuronal populations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Chaochao; Duan, Jicheng; Liu, Tao

Human biofluids, especially blood plasma or serum, hold great potential as the sources of candidate biomarkers for various diseases; however, the enormous dynamic range of protein concentrations in biofluids represents a significant analytical challenge for detecting promising low-abundance proteins. Over the last decade, various immunoaffinity chromatographic methods have been developed and routinely applied for separating low-abundance proteins from the high- and moderate-abundance proteins, thus enabling much more effective detection of low-abundance proteins. Herein, we review the advances of immunoaffinity separation methods and their contributions to the proteomic applications in human biofluids. The limitations and future perspectives of immunoaffinity separation methodsmore » are also discussed.« less

The Economic Importance of Human Capital in Modernization.

ERIC Educational Resources Information Center

Schultz, Theodore W.

1993-01-01

Human capital invests in new forms of physical capital, hence, human capital is key to economic progress. Lists eight attributes of human capital; for example, human capital cannot be separated from person who has it, and human capital is not visible. Human capital is necessary component when attempting to improve a person's income and welfare in…

Air cathode structure manufacture

DOEpatents

Momyer, William R.; Littauer, Ernest L.

1985-01-01

An improved air cathode structure for use in primary batteries and the like. The cathode structure includes a matrix active layer, a current collector grid on one face of the matrix active layer, and a porous, nonelectrically conductive separator on the opposite face of the matrix active layer, the collector grid and separator being permanently bonded to the matrix active layer. The separator has a preselected porosity providing low IR losses and high resistance to air flow through the matrix active layer to maintain high bubble pressure during operation of the battery. In the illustrated embodiment, the separator was formed of porous polypropylene. A thin hydrophobic film is provided, in the preferred embodiment, on the current collecting metal grid.

Human embryonic stem cells fail to activate CHK1 and commit to apoptosis in response to DNA replication stress.

PubMed

Desmarais, Joëlle A; Hoffmann, Michele J; Bingham, Gregg; Gagou, Mary E; Meuth, Mark; Andrews, Peter W

2012-07-01

Pluripotent cells of the early embryo, to which embryonic stem cells (ESCs) correspond, give rise to all the somatic cells of the developing fetus. Any defects that occur in their genome or epigenome would have devastating consequences. Genetic and epigenetic change in human ESCs appear to be an inevitable consequence of long-term culture, driven by selection of variant cells that have a higher propensity for self-renewal rather than either differentiation or death. Mechanisms underlying the potentially separate events of mutation and subsequent selection of variants are poorly understood. Here, we show that human ESCs and their malignant counterpart, embryonal carcinoma (EC) cells, both fail to activate critical S-phase checkpoints when exposed to DNA replication inhibitors and commit to apoptosis instead. Human ESCs and EC cells also fail to form replication protein A, γH2AX, or RAD51 foci or load topoisomerase (DNA) II binding protein 1 onto chromatin in response to replication inhibitors. Furthermore, direct measurements of single-stranded DNA (ssDNA) show that these cells fail to generate the ssDNA regions in response to replication stress that are necessary for the activation of checkpoints and the initiation of homologous recombination repair to protect replication fork integrity and restart DNA replication. Taken together, our data suggest that pluripotent cells control genome integrity by the elimination of damaged cells through apoptosis rather than DNA repair, and therefore, mutations or epigenetic modifications resulting in an imbalance in cell death control could lead to genetic instability. Copyright © 2012 AlphaMed Press.

Some data about the relationship between ths human state and external perturbations of geomagnetic field

NASA Astrophysics Data System (ADS)

Dimitrova, S.; Stoilova, I.; Yanev, T.

The influence of solar activity changes and related to them geomagnetic field variations on human health is confirmed in a lot of publications but the investigations in this area are still sporadic and incomplete because of the fact that it is difficult to separate the geomagnetic influence from the environmental factor complex, which influence the human life activity. That is why we have studied the influence of changes in geomagnetic activity on human physiological, psycho-physiological parameters and behavioural reactions. In this article we looked for influence of changes in GMA on the systolic and diastolic blood pressure and pulse-rate. We examined 54 volunteers. 26 persons of them had some cardio-vascular or blood pressure disturbances. The registrations were performed every day at one and the same time for each person during the period 1.10 - 10.11.2001. Four-way analysis of variance (MANOVA method) with factors: GMA, day, sex and cardiovascular pathology was performed. GMA was divided into four levels according to the Kp- and Ap-index values. The days examined were divided into six levels in relation to the day with increased GMA. Factor "cardiovascular pathology" was divided into two levels: healthy subjects and subjects that had some cardio -vascular or blood pressure disturbances. When we employed four-way analysis of variance, the influence of some of the factors on the physiological parameters examined turned out to be statistically significant at p<0.05. Our investigations indicate that most of the persons examined irrespectively to their status could be sensitive to the geomagnetic disturbances.

Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes.

PubMed

Cittaro, Davide; Lampis, Valentina; Luchetti, Alessandra; Coccurello, Roberto; Guffanti, Alessandro; Felsani, Armando; Moles, Anna; Stupka, Elia; D' Amato, Francesca R; Battaglia, Marco

2016-04-28

Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory and emotional hypersensitivity to CO2 marks separation anxiety and panic disorders, and is enhanced by early-life adversities. Mice exposed to the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened separation anxiety and hyperventilation to 6% CO2-enriched air. Gene-environment interactions affect CO2 hypersensitivity in both humans and mice. We therefore hypothesised that epigenetic modifications and increased expression of genes involved in pH-detection could explain these relationships. Medullae oblongata of RCF- and normally-reared female outbred mice were assessed by ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications, and by SAGE for differential gene expression. Integration of multiple experiments by network analysis revealed an active component of 148 genes pointing to the mTOR signalling pathway and nociception. Among these genes, Asic1 showed heightened mRNA expression, coherent with RCF-mice's respiratory hypersensitivity to CO2 and altered nociception. Functional enrichment and mRNA transcript analyses yielded a consistent picture of enhancement for several genes affecting chemoception, neurodevelopment, and emotionality. Particularly, results with Asic1 support recent human findings with panic and CO2 responses, and provide new perspectives on how early adversities and genes interplay to affect key components of panic and related disorders.

Polarized Ends of Human Macula Densa Cells: Ultrastructural Investigation and Morphofunctional Correlations.

PubMed

Cangiotti, Angela Maria; Lorenzi, Teresa; Zingaretti, Maria Cristina; Fabri, Mara; Morroni, Manrico

2018-05-01

The morphology of the kidney macula densa (MD) has extensively been investigated in animals, whereas human studies are scanty. We studied the fine structure of human MD cells focusing on their apical and basal ends and correlating structure and function. The MD region was examined by transmission electron microscopy in six renal biopsies from patients with kidney disease. Ultrastructural analysis of MD cells was performed on serial sections. MD cells show two polarized ends. The apical portion is characterized by a single, immotile cilium associated with microvilli; apically, cells are joined by adhering junctions. In the basal portion, the cytoplasm contains small, dense granules and numerous, irregular cytoplasmic projections extending to the adjacent extraglomerular mesangium. The projections often contain small, dense granules. A reticulated basement membrane around MD cells separates them from the extraglomerular mesangium. Although the fact that tissue specimens came from patients with kidney disease mandates extreme caution, ultrastructural examination confirmed that MD cells have sensory features due to the presence of the primary cilium, that they are connected by apical adhering junctions forming a barrier that separates the tubular flow from the interstitium, and that they present numerous basal interdigitations surrounded by a reticulated basement membrane. Conceivably, the latter two features are related to the functional activity of the MD. The small, dense granules in the basal cytoplasm and in cytoplasmic projections are likely related to the paracrine function of MD cells. Anat Rec, 301:922-931, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Clinical evaluation of the radiolanthanide terbium-152: first-in-human PET/CT with 152Tb-DOTATOC.

PubMed

Baum, Richard P; Singh, Aviral; Benešová, Martina; Vermeulen, Christiaan; Gnesin, Silvano; Köster, Ulli; Johnston, Karl; Müller, Dirk; Senftleben, Stefan; Kulkarni, Harshad R; Türler, Andreas; Schibli, Roger; Prior, John O; van der Meulen, Nicholas P; Müller, Cristina

2017-10-31

The existence of theragnostic pairs of radionuclides allows the preparation of radiopharmaceuticals for diagnostic and therapeutic purposes. Radiolanthanides, such as 177 Lu, are successfully used for therapeutic purposes; however, a perfect diagnostic match is currently not available for clinical use. A unique, multi-disciplinary study was performed using 152 Tb (T 1/2 = 17.5 h, Eβ + average = 1140 keV, Iβ + = 20.3%), which resulted in the first-in-human PET/CT images with this promising radionuclide. For this purpose, 152 Tb was produced via a spallation process followed by mass separation at ISOLDE, CERN. The chemical separation and quality control, performed at PSI, resulted in a pure product in sufficient yields. Clinical PET phantom studies revealed an increased image noise level, because of the smaller β + branching ratio of 152 Tb as compared to standard PET nuclides at matched activity concentrations; however, the expected recovery would be comparable at matched signal-to-noise ratios in clinical PET. 152 Tb was used for labeling DOTATOC, at Zentralklinik Bad Berka, and administered to a patient for a first-in-human clinical study. PET scans were performed over a period of 24 h, allowing the visualization of even small metastases with increased tumor-to-background contrast over time. Based on the results obtained in this work, it can be deduced that PET/CT imaging with 152 Tb-labeled targeting agents has promise for clinical application and may be particularly interesting for pre-therapeutic dosimetry.

Charles Darwin's emotional expression "experiment" and his contribution to modern neuropharmacology.

PubMed

Snyder, Peter J; Kaufman, Rebecca; Harrison, John; Maruff, Paul

2010-04-08

In the late 1860s and early 1870s, Darwin had corresponded with the French physician and physiologist, G. B. A. Duchenne, regarding Duchenne's experimental manipulation of human facial expression of emotion, by applying Galvanic electrical stimulation directly to facial muscles. Duchenne had produced a set of over 60 photographic plates to illustrate his view that there are different muscles in the human face that are separately responsible for each individual emotion. Darwin studied this material very carefully and he received permission from Duchenne in 1871 to reproduce several of these images in The Expression of the Emotions in Man and Animals (1872). Darwin had doubted Duchenne's view that there were individual muscle groups that mediate the expression of dozens of separable emotions, and he wondered whether there might instead be a fewer set of core emotions that are expressed with great stability worldwide and across cultures. Prompted by his doubts regarding the veracity of Duchenne's model, Darwin conducted what may have been the first-ever single-blind study of the recognition of human facial expression of emotion. This single experiment was a little-known forerunner for an entire modern field of study with contemporary clinical relevance. Moreover, his specific question about cross-cultural recognition of the cardinal emotions in faces is a topic that is being actively studied (in the twenty-first century) with the hope of developing novel biomarkers to aid the discovery of new therapies for the treatment of schizophrenia, autism, and other neuropsychiatric diseases.

Characterization of the human pH- and PKA-activated ClC-2G(2 alpha) Cl- channel.

PubMed

Sherry, A M; Stroffekova, K; Knapp, L M; Kupert, E Y; Cuppoletti, J; Malinowska, D H

1997-08-01

A ClC-2G(2 alpha) Cl- channel was identified to be present in human lung and stomach, and a partial cDNA for this Cl- channel was cloned from a human fetal lung library. A full-length expressible human ClC-2G(2 alpha) cDNA was constructed by ligation of mutagenized expressible rabbit ClC-2G(2 alpha) cDNA with the human lung ClC-2G(2 alpha) cDNA, expressed in oocytes, and characterized at the single-channel level. Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) treatment increased the probability of opening of the channel (Po). After PKA activation, the channel exhibited a linear (r = 0.99) current-voltage curve with a slope conductance of 22.1 +/- 0.8 pS in symmetric 800 mM tetraethylammonium chloride (TEACl; pH 7.4). Under fivefold gradient conditions of TEACl, a reversal potential of +21.5 +/- 2.8 mV was measured demonstrating anion-to-cation discrimination. As previously demonstrated for the rabbit ClC-2G(2 alpha) Cl- channel, the human analog, hClC-2G(2 alpha), was active at pH 7.4 as well as when the pH of the extracellular face of the channel (trans side of the bilayer; pHtrans) was asymmetrically reduced to pH 3.0. The extent of PKA activation was dependent on pHtrans. With PKA treatment, Po increased fourfold with a pHtrans of 7.4 and eightfold with a pHtrans of 3.0. Effects of sequential PKA addition followed by pHtrans reduction on the same channel suggested that the PKA- and pH-dependent increases in channel Po were separable and cumulative. Northern analysis showed ClC-2G(2 alpha) mRNA to be present in human adult and fetal lung and adult stomach, and quantitative reverse transcriptase-polymerase chain reaction showed this channel to be present in the adult human lung and stomach at about one-half the level found in fetal lung. The findings of the present study suggest that the ClC-2G(2 alpha) Cl- channel may play an important role in Cl- transport in the fetal and adult human lung.

Contribution of nonesterified fatty acids to mitogen-activated protein kinase activation in human skeletal muscle during endurance exercise.

PubMed

Zbinden-Foncea, Hermann; van Loon, Luc J C; Raymackers, Jean-Marc; Francaux, Marc; Deldicque, Louise

2013-06-01

Mitogen-activated protein kinase (MAPK) pathways are activated in skeletal muscle during endurance exercise, but the upstream molecular events are incompletely resolved. As an increase in plasma nonesterified fatty acids (NEFA) is a common feature of long-lasting exercise, the authors tested the hypothesis that NEFA contribute to the activation of MAPK during endurance exercise. Acipimox was used before and during endurance exercise to prevent the elevation of plasma NEFA levels in healthy subjects and patients with diabetes. In 2 separate studies, healthy subjects cycled for 2 hr and patients with diabetes for 1 hr at 50% Wmax. In control conditions, plasma NEFA concentrations increased from 0.35 to 0.90 mM during exercise in healthy subjects and from 0.55 to 0.70 mM in patients with diabetes (p < .05). Phosphorylation states of extracellularly regulated kinase 1 and 2 (ERK1/2), p38, and c-Jun NH2-terminal kinases (JNK) were significantly increased after exercise in the vastus lateralis in both groups. Acipimox blocked the increase in plasma NEFA concentrations and almost completely repressed any rise in ERK1/2 and p38 but not in JNK. In conclusion, the data support a role for plasma NEFA in the activation of p38 and ERK1/2 in skeletal-muscle tissue of healthy and diabetic subjects during endurance exercise. Further investigation will be required to determine the molecular link between NEFA and MAPK activation during exercise in human skeletal muscle.

Circadian variations of interferon-induced enhancement of human natural killer (NK) cell activity.

PubMed

Gatti, G; Cavallo, R; Sartori, M L; Carignola, R; Masera, R; Delponte, D; Salvadori, A; Angeli, A

1988-01-01

We searched for circadian changes in the enhancement of the NK activity after exposure to IFN-gamma of peripheral blood mononuclear (PBM) cells obtained serially throughout the 24-h cycle. In August-October 1986, blood was drawn from 7 healthy, diurnally active and nocturnally resting male volunteers (22-34 yr) at 4-h intervals for 24 h starting at 08:00. PBM cells were immediately separated and assayed for NK cell activity, using K 562 cultured cells as a target in a 4-h 51Cr release assay after prior incubation for 20 h with buffer or 300 IU rIFN-gamma. Circadian variations of the spontaneous NK cell cytotoxicity were apparent; the activity was at its maximum at the end of the night or in the early morning and then declined in the afternoon. The 24-h rhythmic pattern was validated with statistical significance by the Cosinor method (p less than 0.02; acrophase 04:22). Maximum enhancement by IFN-gamma was attained in the second part of the night or in the early morning, i.e. in phase with the peak of the spontaneous NK cell activity. A significant circadian rhythm of the percent increase above control levels was validated by the Cosinor method (p less than 0.01; acrophase 04:03). Our findings may be of relevance to a better understanding of the mechanisms of control of human NK activity and warrant consideration as an approach to improve the effectiveness of time-qualified immunotherapy.

Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects

PubMed Central

Tripathi, Siddhartha; Kumar, Y. V. BalaVarun; Agrawal, Amit; Prabhakar, Amit; Joshi, Suhas S.

2016-01-01

In this research work, we present a simple and efficient passive microfluidic device for plasma separation from pure blood. The microdevice has been fabricated using conventional photolithography technique on a single layer of polydimethylsiloxane, and has been extensively tested on whole blood and enhanced (upto 62%) hematocrit levels of human blood. The microdevice employs elevated dimensions of about 100 μm; such elevated dimensions ensure clog-free operation of the microdevice and is relatively easy to fabricate. We show that our microdevice achieves almost 100% separation efficiency on undiluted blood in the flow rate range of 0.3 to 0.5 ml/min. Detailed biological characterization of the plasma obtained from the microdevice is carried out by testing: proteins by ultra-violet spectrophotometric method, hCG (human chorionic gonadotropin) hormone, and conducting random blood glucose test. Additionally, flow cytometry study has also been carried on the separated plasma. These tests attest to the high quality of plasma recovered. The microdevice developed in this work is an outcome of extensive experimental research on understanding the flow behavior and separation phenomenon of blood in microchannels. The microdevice is compact, economical and effective, and is particularly suited in continuous flow operations. PMID:27279146

Simultaneous chromatic and luminance human electroretinogram responses

PubMed Central

Parry, Neil R A; Murray, Ian J; Panorgias, Athanasios; McKeefry, Declan J; Lee, Barry B; Kremers, Jan

2012-01-01

The parallel processing of information forms an important organisational principle of the primate visual system. Here we describe experiments which use a novel chromatic–achromatic temporal compound stimulus to simultaneously identify colour and luminance specific signals in the human electroretinogram (ERG). Luminance and chromatic components are separated in the stimulus; the luminance modulation has twice the temporal frequency of the chromatic modulation. ERGs were recorded from four trichromatic and two dichromatic subjects (1 deuteranope and 1 protanope). At isoluminance, the fundamental (first harmonic) response was elicited by the chromatic component in the stimulus. The trichromatic ERGs possessed low-pass temporal tuning characteristics, reflecting the activity of parvocellular post-receptoral mechanisms. There was very little first harmonic response in the dichromats’ ERGs. The second harmonic response was elicited by the luminance modulation in the compound stimulus and showed, in all subjects, band-pass temporal tuning characteristic of magnocellular activity. Thus it is possible to concurrently elicit ERG responses from the human retina which reflect processing in both chromatic and luminance pathways. As well as providing a clear demonstration of the parallel nature of chromatic and luminance processing in the human retina, the differences that exist between ERGs from trichromatic and dichromatic subjects point to the existence of interactions between afferent post-receptoral pathways that are in operation from the earliest stages of visual processing. PMID:22586211

Human alpha-defensin-1 protects cells from intoxication with Clostridium perfringens iota toxin.

PubMed

Fischer, Stephan; Popoff, Michel R; Barth, Holger

2018-03-01

Iota toxin is produced by Clostridium perfringens type E strains and associated with diarrhea in cattle and lambs. This binary protein toxin comprises the enzyme component iota a (Ia), which ADP-ribosylates G-actin, and the separate transport component iota b (Ib), which delivers Ia into the cytosol of target cells. Ib binds to cell receptors and forms biologically active toxin complexes with Ia, which cause rounding of adherent cells due to the destruction of the actin cytoskeleton. Here, we report that the human peptide α-defensin-1 protects cultured cells including human colon cells from intoxication with iota toxin. In contrast, the related ß-defensin-1 had no effect, indicating a specific mode of action. The α-defensin-1 did not inhibit ADP-ribosylation of actin by Ia in vitro. Pretreatment of Ib with α-defensin-1 prior to addition of Ia prevented intoxication. Additionally, α-defensin-1 protected cells from cytotoxic effects mediated by Ib in the absence of Ia, implicating that α-defensin-1 interacts with Ib to prevent the formation of biologically active iota toxin on cells. In conclusion, the findings contribute to a better understanding of the functions of α-defensin-1 and suggest that this human peptide might be an attractive starting point to develop novel pharmacological options to treat/prevent diseases associated with iota toxin-producing Clostridium perfringens strains.

Adaptive changes in the neuromagnetic response of the primary and association somatosensory areas following repetitive tactile hand stimulation in humans

PubMed Central

Popescu, Anda; Barlow, Steven; Venkatesan, Lalit; Wang, Jingyan; Popescu, Mihai

2014-01-01

Cortical adaptation in the primary somatosensory cortex (SI) has been probed using different stimulation modalities and recording techniques, in both human and animal studies. In contrast, considerably less knowledge has been gained about the adaptation profiles in other areas of the cortical somatosensory network. Using magnetoencephalography, we examined the patterns of short-term adaptation for evoked responses in SI and somatosensory association areas during tactile stimulation applied to the glabrous skin of the right hand. Cutaneous stimuli were delivered as trains of serial pulses with a constant frequency of 2 Hz and 4 Hz in separate runs, and a constant inter-train interval of 5 s. The unilateral stimuli elicited transient responses to the serial pulses in the train, with several response components that were separated by Independent Component Analysis. Subsequent neuromagnetic source reconstruction identified regional generators in the contralateral SI and somatosensory association areas in the posterior parietal cortex (PPC). Activity in the bilateral secondary somatosensory cortex (i.e. SII/PV) was also identified, although less consistently across subjects. The dynamics of the evoked activity in each area and the frequency-dependent adaptation effects were assessed from the changes in the relative amplitude of serial responses in each train. We show that the adaptation profiles in SI and PPC can be quantitatively characterized from neuromagnetic recordings using tactile stimulation, with the sensitivity to repetitive stimulation increasing from SI to PPC. A similar approach for SII/PV has proven less straightforward, potentially due to the selective nature of these areas to respond predominantly to certain stimuli. PMID:22331631

Phase separation and large deviations of lattice active matter

NASA Astrophysics Data System (ADS)

Whitelam, Stephen; Klymko, Katherine; Mandal, Dibyendu

2018-04-01

Off-lattice active Brownian particles form clusters and undergo phase separation even in the absence of attractions or velocity-alignment mechanisms. Arguments that explain this phenomenon appeal only to the ability of particles to move persistently in a direction that fluctuates, but existing lattice models of hard particles that account for this behavior do not exhibit phase separation. Here we present a lattice model of active matter that exhibits motility-induced phase separation in the absence of velocity alignment. Using direct and rare-event sampling of dynamical trajectories, we show that clustering and phase separation are accompanied by pronounced fluctuations of static and dynamic order parameters. This model provides a complement to off-lattice models for the study of motility-induced phase separation.

Automated Microfluidic Instrument for Label-Free and High-Throughput Cell Separation.

PubMed

Zhang, Xinjie; Zhu, Zhixian; Xiang, Nan; Long, Feifei; Ni, Zhonghua

2018-03-20

Microfluidic technologies for cell separation were reported frequently in recent years. However, a compact microfluidic instrument enabling thoroughly automated cell separation is still rarely reported until today due to the difficult hybrid between the macrosized fluidic control system and the microsized microfluidic device. In this work, we propose a novel and automated microfluidic instrument to realize size-based separation of cancer cells in a label-free and high-throughput manner. Briefly, the instrument is equipped with a fully integrated microfluidic device and a set of robust fluid-driven and control units, and the instrument functions of precise fluid infusion and high-throughput cell separation are guaranteed by a flow regulatory chip and two cell separation chips which are the key components of the microfluidic device. With optimized control programs, the instrument is successfully applied to automatically sort human breast adenocarcinoma cell line MCF-7 from 5 mL of diluted human blood with a high recovery ratio of ∼85% within a rapid processing time of ∼23 min. We envision that our microfluidic instrument will be potentially useful in many biomedical applications, especially cell separation, enrichment, and concentration for the purpose of cell culture and analysis.

A sensitive and reproducible fluorescent-based HPLC assay to measure the activity of acid as well as neutral beta-glucocerebrosidases.

PubMed

Hayashi, Yasuhiro; Zama, Kouta; Abe, Eriko; Okino, Nozomu; Inoue, Takehiko; Ohno, Kousaku; Ito, Makoto

2008-12-01

The activity of lysosomal acid beta-glucocerebrosidase (AGC, EC 3.2.1.45), which hydrolyzes the O-glycosidic linkage between D-glucose and ceramide of glucosylceramide (GlcCer), is a marker for the diagnosis of Gaucher disease because the disease is caused by dysfunction of AGC due to mutations in the gene. The activity of AGC is potently inhibited by conduritol B epoxide (CBE), whereas CBE-insensitive nonlysosomal neutral beta-glucocerebrosidase (NGC) activities have been found in various vertebrates, including humans. We report here a new reliable method to determine AGC as well as NGC activities using normal-phase high-performance liquid chromatography (HPLC) and NBD (4-nitrobenzo-2-oxa-1,3-diazole)- or BODIPY (4,4-difluoro-4-boro-3a,4a-diaza-s-indacene)-labeled GlcCer as a substrate. The reaction products of the enzymes, C6-NBD-ceramide and C12-BODIPY-ceramide, were clearly separated from the corresponding substrates on a normal-phase column within 5 min using a different solvent system. Reaction products could be detected quantitatively at concentrations ranging from 50 fmol to 50 pmol for C6-NBD-ceramide and from 10 fmol to 5 pmol for C12-BODIPY-ceramide. V(max)/K(m) values of human fibroblast AGC for fluorescent GlcCer were much higher than those for 4-methylumbelliferyl-beta-d-glucoside (4MU-Glc), which is used prevalently for Gaucher disease diagnosis. As a result, AGC activity was detected quantitatively using fluorescent GlcCer, but not 4MU-Glc, using 5 microl of human serum or 1 x 10(4) cultured human fibroblasts. The current method clearly showed the decrease of AGC activities in fibroblasts and serum from the patient with Gaucher disease compared with normal individuals, suggesting that the method is applicable for the diagnosis of Gaucher disease. Furthermore, this method was found to be useful for measuring the activities of nonlysosomal NGC of various cells and tissues in the presence of CBE.

Thioredoxin, thioredoxin reductase, and alpha-crystallin revive inactivated glyceraldehyde 3-phosphate dehydrogenase in human aged and cataract lens extracts.

PubMed

Yan, Hong; Lou, Marjorie F; Fernando, M Rohan; Harding, John J

2006-10-02

To investigate whether mammalian thioredoxin (Trx) and thioredoxin reductase (TrxR), with or without alpha-crystallin can revive inactivated glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in both the cortex and nucleus of human aged clear and cataract lenses. The lens cortex (including capsule-epithelium) and the nucleus were separated from human aged clear and cataract lenses (grade II and grade IV) with similar average age. The activity of GAPDH in the water-soluble fraction after incubation with or without Trx or/and TrxR for 60 min at 30 degrees C was measured spectrophotometrically. In addition, the effect of a combination of Trx/TrxR and bovine lens alpha-crystallin was investigated. GAPDH activity was lower in the nucleus of clear lenses than in the cortex, and considerably diminished in the cataractous lenses, particularly in the nucleus of cataract lenses grade IV. Trx and TrxR were able to revive the activity of GAPDH markedly in both the cortex and nucleus of the clear and cataract lenses. The percentage increase of activity in the cortex of the clear lenses was less than that of the nucleus in the presence of Trx and TrxR, whereas it was opposite in the cataract lenses. The revival of activity in both the cortex and nucleus from the cataract lenses grade II was higher than that of the grade IV. Moreover, Trx alone, but not TrxR, efficiently enhanced GAPDH activity. The combination of Trx and TrxR had greater effect than that of either alone. In addition, alpha(L)-crystallin enhanced the activity in the cortex of cataract grade II with Trx and TrxR present. However, it failed to provide a statistically significant increase of activity in the nucleus. This is the first evidence to show that mammalian Trx and TrxR are able to revive inactivated GAPDH in human aged clear and cataract lenses, and alpha-crystallin helped this effect. The inactivation of GAPDH during aging and cataract development must be caused in part by disulphide formation and in part by unfolding, and can be recovered by reducing agents and a molecular chaperone.

21 CFR 13.15 - Separation of functions; ex parte communications; administrative support.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Separation of functions; ex parte communications... HUMAN SERVICES GENERAL PUBLIC HEARING BEFORE A PUBLIC BOARD OF INQUIRY General Provisions § 13.15 Separation of functions; ex parte communications; administrative support. (a) The proceeding of a Board are...

Air-Ground Integration Experiment

DOT National Transportation Integrated Search

2002-01-01

could potentially shift aircraft separation responsibility from air traffic controllers to flight crews creating a'shared-separation' : authority environment Areal-time, human-in-the-loop study was conducted using facilities at NASA Ames Research Cen...

Nitrogen Mustard-Induced Corneal Injury Involves DNA Damage and Pathways Related to Inflammation, Epithelial-Stromal Separation, and Neovascularization.

PubMed

Goswami, Dinesh G; Tewari-Singh, Neera; Dhar, Deepanshi; Kumar, Dileep; Agarwal, Chapla; Ammar, David A; Kant, Rama; Enzenauer, Robert W; Petrash, J Mark; Agarwal, Rajesh

2016-02-01

To evaluate the toxic effects and associated mechanisms in corneal tissue exposed to the vesicating agent, nitrogen mustard (NM), a bifunctional alkylating analog of the chemical warfare agent sulfur mustard. Toxic effects and associated mechanisms were examined in maximally affected corneal tissue using corneal cultures and human corneal epithelial (HCE) cells exposed to NM. Analysis of ex vivo rabbit corneas showed that NM exposure increased apoptotic cell death, epithelial thickness, epithelial-stromal separation, and levels of vascular endothelial growth factor, cyclooxygenase 2, and matrix metalloproteinase-9. In HCE cells, NM exposure resulted in a dose-dependent decrease in cell viability and proliferation, which was associated with DNA damage in terms of an increase in p53 ser15, total p53, and H2A.X ser139 levels. NM exposure also induced caspase-3 and poly ADP ribose polymerase cleavage, suggesting their involvement in NM-induced apoptotic death in the rabbit cornea and HCE cells. Similar to rabbit cornea, NM exposure caused an increase in cyclooxygenase 2, matrix metalloproteinase-9, and vascular endothelial growth factor levels in HCE cells, indicating a role of these molecules and related pathways in NM-induced corneal inflammation, epithelial-stromal separation, and neovascularization. NM exposure also induced activation of activator protein 1 transcription factor proteins and upstream signaling pathways including mitogen-activated protein kinases and Akt protein kinase, suggesting that these could be key factors involved in NM-induced corneal injury. Results from this study provide insight into the molecular targets and pathways that could be involved in NM-induced corneal injuries laying the background for further investigation of these pathways in vesicant-induced ocular injuries, which could be helpful in the development of targeted therapies.

Determination of lipoic acid in human urine by capillary zone electrophoresis.

PubMed

Kubalczyk, Paweł; Głowacki, Rafał

2017-07-01

Fast, simple, and accurate CE method enabling determination of lipoic acid (LA) in human urine has been developed and validated. LA is a disulfide-containing natural compound absorbed from the organism's diet. Due to powerful antioxidant activity, LA has been used for prevention and treatment of various diseases and disorders, e.g. cardiovascular diseases, neurodegenerative disorders, and cancer. The proposed analytical procedure consists of liquid-liquid sample extraction, reduction of LA with tris(2-carboxyethyl)phosphine, derivatization with 1-benzyl-2-chloropyridinium bromide (BCPB) followed by field amplified sample injection stacking, capillary zone electrophoresis separation, and ultraviolet-absorbance detection of LA-BCPB derivative at 322 nm. Effective baseline electrophoretic separation was achieved within 6 min under the separation voltage of 20 kV (∼80 μA) using a standard fused-silica capillary (effective length 51.5 cm, 75 μm id) and BGE consisted of 0.05 mol/L borate buffer adjusted to pH 9. The experimentally determined limit of detection for LA in urine was 1.2 μmol/L. The calibration curve obtained for LA in urine showed linearity in the range 2.5-80 μmol/L, with R 2 0.9998. The relative standard deviation of the points of the calibration curve was lower than 10%. The analytical procedure was successfully applied to analysis of real urine samples from seven healthy volunteers who received single 100 mg dose of LA. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human and rat liver phenol sulfotransferase: structure-activity relationships for phenolic substrates.

PubMed

Campbell, N R; Van Loon, J A; Sundaram, R S; Ames, M M; Hansch, C; Weinshilboum, R

1987-12-01

Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of many phenolic drugs. Human liver contains thermostable (TS) and thermolabile forms of PST. Ion exchange chromatography shows that two isozymes of TS PST (peaks I and II) are present in human liver preparations. Rat liver contains four forms of PST that can be separated by ion exchange chromatography. Quantitative structure-activity relationship (QSAR) analysis was used to study phenolic substrates for both human and rat liver PST. Thirty-six substituted phenols were tested as substrates for partially purified human liver TS PST peak I. QSAR analysis resulted in derivation of the following equation: log 1/Km = 0.92 (+/- 0.18)log P - 1.48 (+/- 0.38)MR'4 - 0.64 (+/- 0.41)MR3 + 1.04 (+/- 0.63)MR2 + 0.67(+/- 0.44) sigma- + 4.03 (+/- 0.42). In this equation Km is the Michaelis constant, P is the octanol-water partition coefficient, MR is the molar refractivity of substituents at the 2-, 3-, and 4-positions, and sigma- is the Hammett constant. Values of log 1/Km calculated with this equation were highly correlated with log 1/Km values (r = 0.950) that were observed experimentally. Nine phenols were also tested as substrates for partially purified human liver TS PST peak II. Log 1/Km values for these compounds were significantly correlated for the two isozymes of TS PST (r = 0.992, p less than 0.001). QSAR analysis was also used to derive equations that described the behavior of phenolic substrates for rat liver PST forms I and II. These equations differed substantially from the equation derived for compounds tested with human liver TS PST peak I. Therefore, the characteristics of the active sites of human liver TS PST peak I and rat liver PST forms I and II appear to differ. Application of these equations may make it possible to predict Km values of phenolic substrates for human liver TS PST and for rat liver PST forms I and II.

Caries protective agents in human milk and bovine milk: an in vitro study.

PubMed

Shetty, Vabitha; Hegde, Amitha M; Nandan, S; Shetty, Suchetha

2011-01-01

To estimate Calcium and Phosphorus withdrawal from hydroxyapatite in the presence of bovine milk and human milk from which the following protective fractions namely Casein, Whey protein, Lactose and Milk fat have been individually removed and to compare the above protective fractions in human and bovine milk. Human milk obtained from lactating mothers in the labor ward of Kshema hospital was subjected to immediate analysis. Bovine milk was obtained from a local dairy. Equal quantities of human milk and bovine milk (1 ml) were separately subjected to the systematic removal of the four milk fractions. As each fraction was removed, the remaining milk samples were subjected to testing. Powdered hydroxyapatite from human dental enamel was subjected to demineralization with the addition of the milk sample under test for 20 minutes. This mixture was then centrifuged. Aliquots of the supernatant were taken for calcium and Phosphorus analysis using photospectrometry. Ten demineralization tests were similarly carried out for every milk fraction for both human and bovine milk separately. Equal samples of whole bovine milk and whole human milk were also subjected to similar testing. The calcium and phosphorus dissolution values were higher when the individual fractions were eliminated from both human milk/enamel samples and bovine milk/enamel samples as compared to the values obtained from whole human milk/whole bovine milk/enamel samples. Further higher calcium and phosphorus dissolution values were observed when the fractions were individually and separately removed from the whole human milk/enamel samples as compared to the corresponding values obtained when these fractions were removed from bovine milk/enamel samples. The evaluated milk fraction in bovine milk namely casein, whey protein, lactose and milk fat were individually more caries protective when compared to the corresponding fractions in human milk.

State of expectancy modulates the neural response to visual food stimuli in humans.

PubMed

Malik, Saima; McGlone, Francis; Dagher, Alain

2011-04-01

Human brain imaging studies demonstrate distributed activation of limbic, paralimbic and sensory systems to food and food-associated cues. Activity in this circuit may be modulated by internal factors, such as hunger, and cognitive factors. Anticipation to eat is one such factor, which likely impacts consummatory behavior. Here, the neural substrates of food expectancy were identified in 10 healthy male participants who underwent two whole-brain functional Magnetic Resonance Imaging scans on separate days. Fasted subjects viewed images of food and scenery, in two counterbalanced states. During one condition, subjects were 'expecting' to eat right after the scan and during the other they were 'not expecting' to eat for 1 h after the scan. Food pictures compared with scenery yielded bilateral activation in visual areas as well as in the left insula and amygdala in both conditions. The left dorsolateral prefrontal cortex, hippocampus and putamen were additionally activated in the 'not expecting' condition while right orbitofrontal cortex activity was enhanced in the 'expecting' condition. These data suggest that cognitive manipulations affect the response to food cues in the prefrontal cortex, in areas involved in the planning and control of motivated behaviors, while the amygdala and insula responded equally in both conditions, consistent with a more basic role in homeostatically driven appetitive behavior. Copyright © 2011 Elsevier Ltd. All rights reserved.

Detailed spatiotemporal brain mapping of chromatic vision combining high-resolution VEP with fMRI and retinotopy.

PubMed

Pitzalis, Sabrina; Strappini, Francesca; Bultrini, Alessandro; Di Russo, Francesco

2018-03-13

Neuroimaging studies have identified so far, several color-sensitive visual areas in the human brain, and the temporal dynamics of these activities have been separately investigated using the visual-evoked potentials (VEPs). In the present study, we combined electrophysiological and neuroimaging methods to determine a detailed spatiotemporal profile of chromatic VEP and to localize its neural generators. The accuracy of the present co-registration study was obtained by combining standard fMRI data with retinotopic and motion mapping data at the individual level. We found a sequence of occipito activities more complex than that typically reported for chromatic VEPs, including feed-forward and reentrant feedback. Results showed that chromatic human perception arises by the combined activity of at the least five parieto-occipital areas including V1, LOC, V8/VO, and the motion-sensitive dorsal region MT+. However, the contribution of V1 and V8/VO seems dominant because the re-entrant activity in these areas was present more than once (twice in V8/VO and thrice in V1). This feedforward and feedback chromatic processing appears delayed compared with the luminance processing. Associating VEPs and neuroimaging measures, we showed for the first time a complex spatiotemporal pattern of activity, confirming that chromatic stimuli produce intricate interactions of many different brain dorsal and ventral areas. © 2018 Wiley Periodicals, Inc.

Screening and Development of New Inhibitors of FtsZ from M. Tuberculosis

PubMed Central

Mathew, Bini; Ross, Larry; Connelly, Michele C.; Lofton, Hava; Rajagopalan, Malini; Guy, R. Kiplin; Reynolds, Robert C.

2016-01-01

A variety of commercial analogs and a newer series of Sulindac derivatives were screened for inhibition of M. tuberculosis (Mtb) in vitro and specifically as inhibitors of the essential mycobacterial tubulin homolog, FtsZ. Due to the ease of preparing diverse analogs and a favorable in vivo pharmacokinetic and toxicity profile of a representative analog, the Sulindac scaffold may be useful for further development against Mtb with respect to in vitro bacterial growth inhibition and selective activity for Mtb FtsZ versus mammalian tubulin. Further discovery efforts will require separating reported mammalian cell activity from both antibacterial activity and inhibition of Mtb FtsZ. Modeling studies suggest that these analogs bind in a specific region of the Mtb FtsZ polymer that differs from human tubulin and, in combination with a pharmacophore model presented herein, future hybrid analogs of the reported active molecules that more efficiently bind in this pocket may improve antibacterial activity while improving other drug characteristics. PMID:27768711

Active peptides from skate (Okamejei kenojei) skin gelatin diminish angiotensin-I converting enzyme activity and intracellular free radical-mediated oxidation.

PubMed

Ngo, Dai-Hung; Ryu, BoMi; Kim, Se-Kwon

2014-01-15

Skin gelatin of skate (Okamejei kenojei) was hydrolyzed using Alcalase, flavourzyme, Neutrase and protamex. It was found that the Alcalase hydrolysate exhibited the highest angiotensin-I converting enzyme (ACE) inhibitory activity. Then, Alcalase hydrolysate was further hydrolyzed with protease and separated by an ultrafiltration membrane system. Finally, two peptides responsible for ACE inhibitory activity were identified to be MVGSAPGVL (829Da) and LGPLGHQ (720Da), with IC50 values of 3.09 and 4.22μM, respectively. Moreover, the free radical-scavenging activity of the purified peptides was determined in human endothelial cells. In addition, the antioxidative mechanism of the purified peptides was evaluated by protein and gene expression levels of antioxidant enzymes. The current study demonstrated that the peptides derived from skate skin gelatin could be used in the food industry as functional ingredients with potent antihypertensive and antioxidant benefits. Copyright © 2013 Elsevier Ltd. All rights reserved.

Isolation, Separation, and Preconcentration of Biologically Active Compounds from Plant Matrices by Extraction Techniques.

PubMed

Raks, Victoria; Al-Suod, Hossam; Buszewski, Bogusław

2018-01-01

Development of efficient methods for isolation and separation of biologically active compounds remains an important challenge for researchers. Designing systems such as organomineral composite materials that allow extraction of a wide range of biologically active compounds, acting as broad-utility solid-phase extraction agents, remains an important and necessary task. Selective sorbents can be easily used for highly selective and reliable extraction of specific components present in complex matrices. Herein, state-of-the-art approaches for selective isolation, preconcentration, and separation of biologically active compounds from a range of matrices are discussed. Primary focus is given to novel extraction methods for some biologically active compounds including cyclic polyols, flavonoids, and oligosaccharides from plants. In addition, application of silica-, carbon-, and polymer-based solid-phase extraction adsorbents and membrane extraction for selective separation of these compounds is discussed. Potential separation process interactions are recommended; their understanding is of utmost importance for the creation of optimal conditions to extract biologically active compounds including those with estrogenic properties.

Impact of Pilot Delay and Non-Responsiveness on the Safety Performance of Airborne Separation

NASA Technical Reports Server (NTRS)

Consiglio, Maria; Hoadley, Sherwood; Wing, David; Baxley, Brian; Allen, Bonnie Danette

2008-01-01

Assessing the safety effects of prediction errors and uncertainty on automationsupported functions in the Next Generation Air Transportation System concept of operations is of foremost importance, particularly safety critical functions such as separation that involve human decision-making. Both ground-based and airborne, the automation of separation functions must be designed to account for, and mitigate the impact of, information uncertainty and varying human response. This paper describes an experiment that addresses the potential impact of operator delay when interacting with separation support systems. In this study, we evaluated an airborne separation capability operated by a simulated pilot. The experimental runs are part of the Safety Performance of Airborne Separation (SPAS) experiment suite that examines the safety implications of prediction errors and system uncertainties on airborne separation assistance systems. Pilot actions required by the airborne separation automation to resolve traffic conflicts were delayed within a wide range, varying from five to 240 seconds while a percentage of randomly selected pilots were programmed to completely miss the conflict alerts and therefore take no action. Results indicate that the strategicAirborne Separation Assistance System (ASAS) functions exercised in the experiment can sustain pilot response delays of up to 90 seconds and more, depending on the traffic density. However, when pilots or operators fail to respond to conflict alerts the safety effects are substantial, particularly at higher traffic densities.

Human recreation affects spatio-temporal habitat use patterns in red deer (Cervus elaphus)

PubMed Central

Coppes, Joy; Burghardt, Friedrich; Hagen, Robert; Suchant, Rudi; Braunisch, Veronika

2017-01-01

The rapid spread and diversification of outdoor recreation can impact on wildlife in various ways, often leading to the avoidance of disturbed habitats. To mitigate human-wildlife conflicts, spatial zonation schemes can be implemented to separate human activities from key wildlife habitats, e.g., by designating undisturbed wildlife refuges or areas with some level of restriction to human recreation and land use. However, mitigation practice rarely considers temporal differences in human-wildlife interactions. We used GPS telemetry data from 15 red deer to study the seasonal (winter vs. summer) and diurnal (day vs. night) variation in recreation effects on habitat use in a study region in south-western Germany where a spatial zonation scheme has been established. Our study aimed to determine if recreation infrastructure and spatial zonation affected red deer habitat use and whether these effects varied daily or seasonally. Recreation infrastructure did not affect home range selection in the study area, but strongly determined habitat use within the home range. The spatial zonation scheme was reflected in both of these two levels of habitat selection, with refuges and core areas being more frequently used than the border zones. Habitat use differed significantly between day and night in both seasons. Both summer and winter recreation trails, and nearby foraging habitats, were avoided during day, whereas a positive association was found during night. We conclude that human recreation has an effect on red deer habitat use, and when designing mitigation measures daily and seasonal variation in human-wildlife interactions should be taken into account. We advocate using spatial zonation in conjunction with temporal restrictions (i.e., banning nocturnal recreation activities) and the creation of suitable foraging habitats away from recreation trails. PMID:28467429

Routine Production of 89Zr Using an Automated Module

DOE PAGES

Wooten, A.; Madrid, Evelyn; Schweitzer, Gordon; ...

2013-07-12

89Zr has emerged as a useful radioisotope for targeted molecular imaging via positron emission tomography (PET) in both animal models and humans. This isotope is particularly attractive for cancer research because its half-life (t 1/2 = 3.27 days) is well-suited for in vivo targeting of macromolecules and nanoparticles to cell surface antigens expressed by cancer cells. Furthermore, 89Zr emits a low-energy positron (E β+,mean = 0.40 MeV), which is favorable for high spatial resolution in PET, with an adequate branching ratio for positron emission (BR = 23%). The demand for 89Zr for research purposes is increasing; however, 89Zr also emitsmore » significant gamma radiation (Γ 15 keV = 6.6 R∙cm 2/mCi∙h), which makes producing large amounts of this isotope by hand unrealistic from a radiation safety standpoint. Fortunately, a straightforward method exists for production of 89Zr by bombarding a natural Y target in a biomedical cyclotron and then separation of 89Zr from the target material by column chromatography. The chemical separation in this method lends itself to remote processing using an automated module placed inside a hot cell. In this work, we have designed, built and commissioned a module that has performed the chemical separation of 89Zr safely and routinely, at activities in excess of 50 mCi, with radionuclidic purity > 99.9% and satisfactory effective specific activity (ESA).« less

Synergistic effect of concanavalin A and Bu-WSA on DNA synthesis in human peripheral blood lymphocytes.

PubMed

Nitta, T; Okumura, S; Nakano, M

1985-02-01

Butanol-extracted water soluble adjuvant (Bu-WSA) obtained from Bacterionema matruchotii was not mitogenic for human peripheral blood mononuclear cells (PBM) but was capable of enhancing (3H) thymidine uptake of T cells stimulated by concanavalin A (Con A) in the presence of B cells or macrophages (M phi) in vitro. The mechanisms of the synergy of Con A and Bu-WSA were studied by using separated cell populations from PBM. Both subfractioned OKT4+ and OKT8+ cells were responsive to co-stimulation by Con A and Bu-WSA in the presence of an accessory cell population. Allogeneic B cells and M phi as well as autologous cells had helper function as accessory cells. Heavy irradiation with gamma-rays did not affect the function of the accessory cells, but previous treatment of B cells with anti-Ig serum plus complement (C) or treatment of M phi with anti-M phi serum plus C deprived them of their function. The treatment of accessory cells with anti-HLA-DR serum, regardless of the presence or absence of C, resulted in loss of their helper function. Cultures in Marbrook-type vessels showed that a mixed cell population of T cells and accessory cells in the lower chamber produced some active factor(s) after co-stimulation with Con A and Bu-WSA, and by passing through the membrane filter separating the chambers, the factor(s) enhanced the proliferation of the Con A-activated T cell population in the upper chamber. The factor(s) was presumed to be interleukin 2 (IL 2), because it supported the growth of IL 2-dependent CTLL cells. These results indicate that the synergy of Con A and Bu-WSA on the proliferative response of human PBM is due to the elevation of growth factor production from T cells stimulated by those mitogens.

Microgravity electrophoresis: A study of the factors that affect free-fluid separation

NASA Technical Reports Server (NTRS)

1985-01-01

Electrophoresis experiments have been performed in the microgravity environment of the Space Shuttle. Test particles (fixed human and rabbit erythrocytes) migrated as expected in a static column and test macromolecules (human serum albumin, ovalbumin, hemoglobin A, and Pneumococcus polysaccharide 6B) migrated as expected in a continuous flow apparatus. The concentrations studied exceeded those that can be used in free-fluid separation and purification processes at unit gravity.

Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus

PubMed Central

Sieger, Tomáš; Serranová, Tereza; Růžička, Filip; Vostatek, Pavel; Wild, Jiří; Šťastná, Daniela; Bonnet, Cecilia; Novák, Daniel; Růžička, Evžen; Urgošík, Dušan; Jech, Robert

2015-01-01

Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson’s disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well. PMID:25713375

Early human symbolic behavior in the Late Pleistocene of Wallacea

PubMed Central

Brumm, Adam; Hakim, Budianto; Ramli, Muhammad; Sumantri, Iwan; Burhan, Basran; Saiful, Andi Muhammad; Siagian, Linda; Suryatman; Sardi, Ratno; Jusdi, Andi; Abdullah; Mubarak, Andi Pampang; Hasliana; Hasrianti; Oktaviana, Adhi Agus; Adhityatama, Shinatria; van den Bergh, Gerrit D.; Aubert, Maxime; Zhao, Jian-xin; Huntley, Jillian; Li, Bo; Roberts, Richard G.; Saptomo, E. Wahyu; Perston, Yinika; Grün, Rainer

2017-01-01

Wallacea, the zone of oceanic islands separating the continental regions of Southeast Asia and Australia, has yielded sparse evidence for the symbolic culture of early modern humans. Here we report evidence for symbolic activity 30,000–22,000 y ago at Leang Bulu Bettue, a cave and rock-shelter site on the Wallacean island of Sulawesi. We describe hitherto undocumented practices of personal ornamentation and portable art, alongside evidence for pigment processing and use in deposits that are the same age as dated rock art in the surrounding karst region. Previously, assemblages of multiple and diverse types of Pleistocene “symbolic” artifacts were entirely unknown from this region. The Leang Bulu Bettue assemblage provides insight into the complexity and diversification of modern human culture during a key period in the global dispersal of our species. It also shows that early inhabitants of Sulawesi fashioned ornaments from body parts of endemic animals, suggesting modern humans integrated exotic faunas and other novel resources into their symbolic world as they colonized the biogeographically unique regions southeast of continental Eurasia. PMID:28373568

SEIPS 2.0: A human factors framework for studying and improving the work of healthcare professionals and patients

PubMed Central

Holden, Richard J.; Carayon, Pascale; Gurses, Ayse P.; Hoonakker, Peter; Hundt, Ann Schoofs; Ozok, A. Ant; Rivera-Rodriguez, A. Joy

2013-01-01

Healthcare practitioners, patient safety leaders, educators, and researchers increasingly recognize the value of human factors/ergonomics and make use of the discipline’s person-centered models of sociotechnical systems. This paper first reviews one of the most widely used healthcare human factors systems models, the Systems Engineering Initiative for Patient Safety (SEIPS) model, and then introduces an extended model, “SEIPS 2.0.” SEIPS 2.0 incorporates three novel concepts into the original model: configuration, engagement, and adaptation. The concept of configuration highlights the dynamic, hierarchical, and interactive properties of sociotechnical systems, making it possible to depict how health-related performance is shaped at “a moment in time.” Engagement conveys that various individuals and teams can perform health-related activities separately and collaboratively. Engaged individuals often include patients, family caregivers, and other non-professionals. Adaptation is introduced as a feedback mechanism that explains how dynamic systems evolve in planned and unplanned ways. Key implications and future directions for human factors research in healthcare are discussed. PMID:24088063

Early human symbolic behavior in the Late Pleistocene of Wallacea.

PubMed

Brumm, Adam; Langley, Michelle C; Moore, Mark W; Hakim, Budianto; Ramli, Muhammad; Sumantri, Iwan; Burhan, Basran; Saiful, Andi Muhammad; Siagian, Linda; Suryatman; Sardi, Ratno; Jusdi, Andi; Abdullah; Mubarak, Andi Pampang; Hasliana; Hasrianti; Oktaviana, Adhi Agus; Adhityatama, Shinatria; van den Bergh, Gerrit D; Aubert, Maxime; Zhao, Jian-Xin; Huntley, Jillian; Li, Bo; Roberts, Richard G; Saptomo, E Wahyu; Perston, Yinika; Grün, Rainer

2017-04-18

Wallacea, the zone of oceanic islands separating the continental regions of Southeast Asia and Australia, has yielded sparse evidence for the symbolic culture of early modern humans. Here we report evidence for symbolic activity 30,000-22,000 y ago at Leang Bulu Bettue, a cave and rock-shelter site on the Wallacean island of Sulawesi. We describe hitherto undocumented practices of personal ornamentation and portable art, alongside evidence for pigment processing and use in deposits that are the same age as dated rock art in the surrounding karst region. Previously, assemblages of multiple and diverse types of Pleistocene "symbolic" artifacts were entirely unknown from this region. The Leang Bulu Bettue assemblage provides insight into the complexity and diversification of modern human culture during a key period in the global dispersal of our species. It also shows that early inhabitants of Sulawesi fashioned ornaments from body parts of endemic animals, suggesting modern humans integrated exotic faunas and other novel resources into their symbolic world as they colonized the biogeographically unique regions southeast of continental Eurasia.

Comparative Cognitive Development

ERIC Educational Resources Information Center

Matsuzawa, Tetsuro

2007-01-01

This paper aims to compare cognitive development in humans and chimpanzees to illuminate the evolutionary origins of human cognition. Comparison of morphological data and life history strongly highlights the common features of all primate species, including humans. The human mother-infant relationship is characterized by the physical separation of…

Two Independent Contributions to Step Variability during Over-Ground Human Walking

PubMed Central

Collins, Steven H.; Kuo, Arthur D.

2013-01-01

Human walking exhibits small variations in both step length and step width, some of which may be related to active balance control. Lateral balance is thought to require integrative sensorimotor control through adjustment of step width rather than length, contributing to greater variability in step width. Here we propose that step length variations are largely explained by the typical human preference for step length to increase with walking speed, which itself normally exhibits some slow and spontaneous fluctuation. In contrast, step width variations should have little relation to speed if they are produced more for lateral balance. As a test, we examined hundreds of overground walking steps by healthy young adults (N = 14, age < 40 yrs.). We found that slow fluctuations in self-selected walking speed (2.3% coefficient of variation) could explain most of the variance in step length (59%, P < 0.01). The residual variability not explained by speed was small (1.5% coefficient of variation), suggesting that step length is actually quite precise if not for the slow speed fluctuations. Step width varied over faster time scales and was independent of speed fluctuations, with variance 4.3 times greater than that for step length (P < 0.01) after accounting for the speed effect. That difference was further magnified by walking with eyes closed, which appears detrimental to control of lateral balance. Humans appear to modulate fore-aft foot placement in precise accordance with slow fluctuations in walking speed, whereas the variability of lateral foot placement appears more closely related to balance. Step variability is separable in both direction and time scale into balance- and speed-related components. The separation of factors not related to balance may reveal which aspects of walking are most critical for the nervous system to control. PMID:24015308

CD146 positive human dental pulp stem cells promote regeneration of dentin/pulp-like structures.

PubMed

Matsui, Mikiko; Kobayashi, Tomoko; Tsutsui, Takeo W

2018-04-01

CD146 and STRO-1 are endothelial biomarkers that are co-expressed on the cellular membranes of blood vessels within human dental pulp tissue. This study characterized the percentage of dentin-like structures produced by CD146-positive (CD146 + ) human dental pulp stem cells (DPSCs), compared with their CD146-negative (CD146 - ) counterparts. DPSC populations were enriched using magnetic-activated cell sorting (MACS), yielding CD146 + and CD146 - cells, as well as mixtures composed of 25% CD146 + cells and 75% CD146 - cells (CD146 +/- ). Cell growth assays indicated that CD146 + cells exhibit an approximate 3-4 h difference in doubling time, compared with CD146 - cells. Cell cycle distributions were determined by flow cytometry analysis. The low percentage of CD146 + cells' DNA content in G 0 /G 1 phase were compared with CD146 - and non-separated cells. In contrast to CD146 - and non-separated cells, prompt mineralization was observed in CD146 + cells. Subsequently, qRT-PCR revealed high mRNA expression of CD146 and Alkaline phosphatase in mineralization-induced CD146 + cells. CD146 + cells were also observed high adipogenic ability by Oil red O staining. Histological examinations revealed an increased area of dentin/pulp-like structures in transplanted CD146 + cells, compared with CD146 - and CD146 +/- cells. Immunohistochemical studies detected dentin matrix protein-1 (DMP1) and dentin sialophosphoprotein (DSPP), as well as human mitochondria, in transplanted DPSCs. Co-expression of CD146 and GFP indicated that CD146 was expressed in transplanted CD146 + cells. CD146 + cells may promote mineralization and generate dentin/pulp-like structures, suggesting a role in self-renewal of stem cells and dental pulp regenerative therapy.

Direct anti-inflammatory effects of granulocyte colony-stimulating factor (G-CSF) on activation and functional properties of human T cell subpopulations in vitro.

PubMed

Malashchenko, Vladimir Vladimirovich; Meniailo, Maxsim Evgenievich; Shmarov, Viacheslav Anatolievich; Gazatova, Natalia Dinislamovna; Melashchenko, Olga Borisovna; Goncharov, Andrei Gennadievich; Seledtsova, Galina Victorovna; Seledtsov, Victor Ivanovich

2018-03-01

We investigated the direct effects of human granulocyte colony-stimulating factor (G-CSF) on functionality of human T-cell subsets. CD3 + T-lymphocytes were isolated from blood of healthy donors by positive magnetic separation. T cell activation with particles conjugated with antibodies (Abs) to human CD3, CD28 and CD2 molecules increased the proportion of cells expressing G-CSF receptor (G-CSFR, CD114) in all T cell subpopulations studied (CD45RA + /CD197 + naive T cells, CD45RA - /CD197 + central memory T cells, CD45RA - /CD197 - effector memory T cells and CD45RA + /CD197 - terminally differentiated effector T cells). Upon T-cell activation in vitro, G-CSF (10.0 ng/ml) significantly and specifically enhanced the proportion of CD114 + T cells in central memory CD4 + T cell compartment. A dilution series of G-CSF (range, 0.1-10.0 ng/ml) was tested, with no effect on the expression of CD25 (interleukin-2 receptor α-chain) on activated T cells. Meanwhile, G-CSF treatment enhanced the proportion of CD38 + T cells in CD4 + naïve T cell, effector memory T cell and terminally differentiated effector T cell subsets, as well as in CD4 - central memory T cells and terminally differentiated effector T cells. G-CSF did not affect IL-2 production by T cells; relatively low concentrations of G-CSF down-regulated INF-γ production, while high concentrations of this cytokine up-regulated IL-4 production in activated T cells. The data obtained suggests that G-CSF could play a significant role both in preventing the development of excessive and potentially damaging inflammatory reactivity, and in constraining the expansion of potentially cytodestructive T cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Infants' Responses to Real Humans and Representations of Humans

ERIC Educational Resources Information Center

Heron, Michelle; Slaughter, Virginia

2010-01-01

Infants' responses to typical and scrambled human body shapes were assessed in relation to the realism of the human body stimuli presented. In four separate experiments, infants were familiarized to typical human bodies and then shown a series of scrambled human bodies on the test. Looking behaviour was assessed in response to a range of different…

Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity.

PubMed

Mesnage, R; Bernay, B; Séralini, G-E

2013-11-16

Pesticides are always used in formulations as mixtures of an active principle with adjuvants. Glyphosate, the active ingredient of the major pesticide in the world, is an herbicide supposed to be specific on plant metabolism. Its adjuvants are generally considered as inert diluents. Since side effects for all these compounds have been claimed, we studied potential active principles for toxicity on human cells for 9 glyphosate-based formulations. For this we detailed their compositions and toxicities, and as controls we used a major adjuvant (the polyethoxylated tallowamine POE-15), glyphosate alone, and a total formulation without glyphosate. This was performed after 24h exposures on hepatic (HepG2), embryonic (HEK293) and placental (JEG3) cell lines. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. The compositions in adjuvants were analyzed by mass spectrometry. Here we demonstrate that all formulations are more toxic than glyphosate, and we separated experimentally three groups of formulations differentially toxic according to their concentrations in ethoxylated adjuvants. Among them, POE-15 clearly appears to be the most toxic principle against human cells, even if others are not excluded. It begins to be active with negative dose-dependent effects on cellular respiration and membrane integrity between 1 and 3ppm, at environmental/occupational doses. We demonstrate in addition that POE-15 induces necrosis when its first micellization process occurs, by contrast to glyphosate which is known to promote endocrine disrupting effects after entering cells. Altogether, these results challenge the establishment of guidance values such as the acceptable daily intake of glyphosate, when these are mostly based on a long term in vivo test of glyphosate alone. Since pesticides are always used with adjuvants that could change their toxicity, the necessity to assess their whole formulations as mixtures becomes obvious. This challenges the concept of active principle of pesticides for non-target species. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Spatial attention increases high-frequency gamma synchronisation in human medial visual cortex.

PubMed

Koelewijn, Loes; Rich, Anina N; Muthukumaraswamy, Suresh D; Singh, Krish D

2013-10-01

Visual information processing involves the integration of stimulus and goal-driven information, requiring neuronal communication. Gamma synchronisation is linked to neuronal communication, and is known to be modulated in visual cortex both by stimulus properties and voluntarily-directed attention. Stimulus-driven modulations of gamma activity are particularly associated with early visual areas such as V1, whereas attentional effects are generally localised to higher visual areas such as V4. The absence of a gamma increase in early visual cortex is at odds with robust attentional enhancements found with other measures of neuronal activity in this area. Here we used magnetoencephalography (MEG) to explore the effect of spatial attention on gamma activity in human early visual cortex using a highly effective gamma-inducing stimulus and strong attentional manipulation. In separate blocks, subjects tracked either a parafoveal grating patch that induced gamma activity in contralateral medial visual cortex, or a small line at fixation, effectively attending away from the gamma-inducing grating. Both items were always present, but rotated unpredictably and independently of each other. The rotating grating induced gamma synchronisation in medial visual cortex at 30-70 Hz, and in lateral visual cortex at 60-90 Hz, regardless of whether it was attended. Directing spatial attention to the grating increased gamma synchronisation in medial visual cortex, but only at 60-90 Hz. These results suggest that the generally found increase in gamma activity by spatial attention can be localised to early visual cortex in humans, and that stimulus and goal-driven modulations may be mediated at different frequencies within the gamma range. Copyright © 2013 Elsevier Inc. All rights reserved.

Getting the word out: neural correlates of enthusiastic message propagation.

PubMed

Falk, Emily B; O'Donnell, Matthew Brook; Lieberman, Matthew D

2012-01-01

What happens in the mind of a person who first hears a potentially exciting idea?We examined the neural precursors of spreading ideas with enthusiasm, and dissected enthusiasm into component processes that can be identified through automated linguistic analysis, gestalt human ratings of combined linguistic and non-verbal cues, and points of convergence/divergence between the two. We combined tools from natural language processing (NLP) with data gathered using fMRI to link the neurocognitive mechanisms that are set in motion during initial exposure to ideas and subsequent behaviors of these message communicators outside of the scanner. Participants' neural activity was recorded as they reviewed ideas for potential television show pilots. Participants' language from video-taped interviews collected post-scan was transcribed and given to an automated linguistic sentiment analysis (SA) classifier, which returned ratings for evaluative language (evaluative vs. descriptive) and valence (positive vs. negative). Separately, human coders rated the enthusiasm with which participants transmitted each idea. More positive sentiment ratings by the automated classifier were associated with activation in neural regions including medial prefrontal cortex; MPFC, precuneus/posterior cingulate cortex; PC/PCC, and medial temporal lobe; MTL. More evaluative, positive, descriptions were associated exclusively with neural activity in temporal-parietal junction (TPJ). Finally, human ratings indicative of more enthusiastic sentiment were associated with activation across these regions (MPFC, PC/PCC, DMPFC, TPJ, and MTL) as well as in ventral striatum (VS), inferior parietal lobule and premotor cortex. Taken together, these data demonstrate novel links between neural activity during initial idea encoding and the enthusiasm with which the ideas are subsequently delivered. This research lays the groundwork to use machine learning and neuroimaging data to study word of mouth communication and the spread of ideas in both traditional and new media environments.

Getting the word out: neural correlates of enthusiastic message propagation

PubMed Central

Falk, Emily B.; O'Donnell, Matthew Brook; Lieberman, Matthew D.

2012-01-01

What happens in the mind of a person who first hears a potentially exciting idea?We examined the neural precursors of spreading ideas with enthusiasm, and dissected enthusiasm into component processes that can be identified through automated linguistic analysis, gestalt human ratings of combined linguistic and non-verbal cues, and points of convergence/divergence between the two. We combined tools from natural language processing (NLP) with data gathered using fMRI to link the neurocognitive mechanisms that are set in motion during initial exposure to ideas and subsequent behaviors of these message communicators outside of the scanner. Participants' neural activity was recorded as they reviewed ideas for potential television show pilots. Participants' language from video-taped interviews collected post-scan was transcribed and given to an automated linguistic sentiment analysis (SA) classifier, which returned ratings for evaluative language (evaluative vs. descriptive) and valence (positive vs. negative). Separately, human coders rated the enthusiasm with which participants transmitted each idea. More positive sentiment ratings by the automated classifier were associated with activation in neural regions including medial prefrontal cortex; MPFC, precuneus/posterior cingulate cortex; PC/PCC, and medial temporal lobe; MTL. More evaluative, positive, descriptions were associated exclusively with neural activity in temporal-parietal junction (TPJ). Finally, human ratings indicative of more enthusiastic sentiment were associated with activation across these regions (MPFC, PC/PCC, DMPFC, TPJ, and MTL) as well as in ventral striatum (VS), inferior parietal lobule and premotor cortex. Taken together, these data demonstrate novel links between neural activity during initial idea encoding and the enthusiasm with which the ideas are subsequently delivered. This research lays the groundwork to use machine learning and neuroimaging data to study word of mouth communication and the spread of ideas in both traditional and new media environments. PMID:23189049

Antibacterial and anticancer activities of acetone extracts from in vitro cultured lichen-forming fungi.

PubMed

Felczykowska, Agnieszka; Pastuszak-Skrzypczak, Alicja; Pawlik, Anna; Bogucka, Krystyna; Herman-Antosiewicz, Anna; Guzow-Krzemińska, Beata

2017-06-07

Lichens that were used in traditional medicine for ages produce numerous secondary metabolites, however our knowledge about biological activities of substances secreted by separated bionts is scarce. The main objectives of this study were to isolate and find optimal conditions for the growth of mycelia from three common lichen-forming fungi, i.e. Caloplaca pusilla, Protoparmeliopsis muralis and Xanthoria parietina and to evaluate antibacterial and antiproliferative activities of their acetone extracts. Agar disc diffusion and broth microdilution methods were used to test antimicrobial activity against six species of bacteria. MTT method, flow cytometry assay and DAPI staining were applied to test antiproliferative activity of selected extracts against MCF-7 (human breast adenocarcinoma), PC-3 (human prostate cancer) and HeLa (human cervix adenocarcinoma) cancer cells. P. muralis strongly inhibited the growth of Gram-positive bacteria, i.e. Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus and Staphylococcus epidermidis (MICs from 6.67 to 100.00 μg mL -1 ). X. parietina grown on PDA and G-LBM media decreased HeLa or MCF-7 cancer cells viability with IC 50 values of about 8 μg mL -1 , while C. pusilla grown on G-LBM medium showed the highest potency in decreasing MCF-7 (7.29 μg mL -1 ), PC-3 (7.96 μg mL -1 ) and HeLa (6.57 μg mL -1 ) cancer cells viability. We also showed induction of apoptosis in HeLa, PC-3 and MCF-7 cell lines treated with increasing concentrations of C. pusilla extract. We showed that selected acetone extracts demonstrated a strong antimicrobial and anticancer effects that suggests that aposymbiotically cultured lichen-forming fungi can be a source of antibacterial and antiproliferative compounds.

The role of human outdoor recreation in shaping patterns of grizzly bear-black bear co-occurrence

PubMed Central

Steenweg, Robin; Shepherd, Brenda; Boyce, Mark S.

2018-01-01

Species’ distributions are influenced by a combination of landscape variables and biotic interactions with other species, including people. Grizzly bears and black bears are sympatric, competing omnivores that also share habitats with human recreationists. By adapting models for multi-species occupancy analysis, we analyzed trail camera data from 192 trail camera locations in and around Jasper National Park, Canada to estimate grizzly bear and black bear occurrence and intensity of trail use. We documented (a) occurrence of grizzly bears and black bears relative to habitat variables (b) occurrence and intensity of use relative to competing bear species and motorised and non-motorised recreational activity, and (c) temporal overlap in activity patterns among the two bear species and recreationists. Grizzly bears were spatially separated from black bears, selecting higher elevations and locations farther from roads. Both species co-occurred with motorised and non-motorised recreation, however, grizzly bears reduced their intensity of use of sites with motorised recreation present. Black bears showed higher temporal activity overlap with recreational activity than grizzly bears, however differences in bear daily activity patterns between sites with and without motorised and non-motorised recreation were not significant. Reduced intensity of use by grizzly bears of sites where motorised recreation was present is a concern given off-road recreation is becoming increasingly popular in North America, and can negatively influence grizzly bear recovery by reducing foraging opportunities near or on trails. Camera traps and multi-species occurrence models offer non-invasive methods for identifying how habitat use by animals changes relative to sympatric species, including humans. These conclusions emphasise the need for integrated land-use planning, access management, and grizzly bear conservation efforts to consider the implications of continued access for motorised recreation in areas occupied by grizzly bears. PMID:29389939

The role of human outdoor recreation in shaping patterns of grizzly bear-black bear co-occurrence.

PubMed

Ladle, Andrew; Steenweg, Robin; Shepherd, Brenda; Boyce, Mark S

2018-01-01

Species' distributions are influenced by a combination of landscape variables and biotic interactions with other species, including people. Grizzly bears and black bears are sympatric, competing omnivores that also share habitats with human recreationists. By adapting models for multi-species occupancy analysis, we analyzed trail camera data from 192 trail camera locations in and around Jasper National Park, Canada to estimate grizzly bear and black bear occurrence and intensity of trail use. We documented (a) occurrence of grizzly bears and black bears relative to habitat variables (b) occurrence and intensity of use relative to competing bear species and motorised and non-motorised recreational activity, and (c) temporal overlap in activity patterns among the two bear species and recreationists. Grizzly bears were spatially separated from black bears, selecting higher elevations and locations farther from roads. Both species co-occurred with motorised and non-motorised recreation, however, grizzly bears reduced their intensity of use of sites with motorised recreation present. Black bears showed higher temporal activity overlap with recreational activity than grizzly bears, however differences in bear daily activity patterns between sites with and without motorised and non-motorised recreation were not significant. Reduced intensity of use by grizzly bears of sites where motorised recreation was present is a concern given off-road recreation is becoming increasingly popular in North America, and can negatively influence grizzly bear recovery by reducing foraging opportunities near or on trails. Camera traps and multi-species occurrence models offer non-invasive methods for identifying how habitat use by animals changes relative to sympatric species, including humans. These conclusions emphasise the need for integrated land-use planning, access management, and grizzly bear conservation efforts to consider the implications of continued access for motorised recreation in areas occupied by grizzly bears.

Effect of tibolone and its principal metabolites (3α- and 3β-hydroxy, 3α-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal and cancerous human breast tissue.

PubMed

Chetrite, Gérard S; Cortes-Prieto, Joaquin; Pasqualini, Jorge R

2011-12-01

Tibolone (Org-OD14) is the active substance of Livial®, a synthetic steroid with the structure 7α,17α-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, possessing weak tissue-specific estrogenic, progestogenic, and androgenic properties, used to treat menopausal complaints. After oral administration, tibolone is extensively metabolized into the 3α-(Org-4904) and 3β-(Org-30126) hydroxy derivatives with estrogenic properties, its 4-ene (Org-OM38) isomer with progestogenic/androgenic activities, and the 3α-sulfate (Org-34322) derivative, a major biologically inactive circulating form. We compared the dose response of tibolone and its metabolites on estrone sulfatase activity [conversion of estrone sulfate (E1S) to estrone (E1)] in normal and cancerous human breast tissues. Tissue minces were incubated with physiological concentrations of [3H]-E1S (5×10-9M) alone or in the presence of tibolone and its metabolites (concentration range: 5×10-7to 5×10-5M) for 4 h. Tritiated E1, estradiol (E2), and E1S were separated and evaluated quantitatively by thin-layer chromatography. The sulfatase activity was significantly higher in cancerous breast but strongly inhibited by tibolone and the different metabolites, whereas 3α- and 3β-hydroxy derivatives were the most potent inhibitors. This very significant inhibitory effect of tibolone and its principal metabolites on the enzyme involved in E2biosynthesis in the human breast provides interesting perspectives to study the biological responses of these compounds in trials with breast cancer patients.

TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules.

PubMed

Liu, Qian; Sun, Jessica D; Wang, Jingli; Ahluwalia, Dharmendra; Baker, Amanda F; Cranmer, Lee D; Ferraro, Damien; Wang, Yan; Duan, Jian-Xin; Ammons, W Steve; Curd, John G; Matteucci, Mark D; Hart, Charles P

2012-06-01

Subregional hypoxia is a common feature of tumors and is recognized as a limiting factor for the success of radiotherapy and chemotherapy. TH-302, a hypoxia-activated prodrug selectively targeting hypoxic regions of solid tumors, delivers a cytotoxic warhead to the tumor, while maintaining relatively low systemic toxicity. The antitumor activity, different dosing sequences, and dosing regimens of TH-302 in combination with commonly used conventional chemotherapeutics were investigated in human tumor xenograft models. Seven chemotherapeutic drugs (docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide) were tested in combination with TH-302 in eleven human xenograft models, including non-small cell lung cancer (NSCLC), colon cancer, prostate cancer, fibrosarcoma, melanoma, and pancreatic cancer. The antitumor activity of docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide was increased when combined with TH-302 in nine out of eleven models tested. Administration of TH-302 2-8 h prior to the other chemotherapeutics yielded superior efficacy versus other sequences tested. Simultaneous administration of TH-302 and chemotherapeutics increased toxicity versus schedules with dosing separations. In a dosing optimization study, TH-302 administered daily at 50 mg/kg intraperitoneally for 5 days per week in the H460 NSCLC model showed the optimal response with minimal toxicity. TH-302 enhances the activity of a wide range of conventional anti-neoplastic agents in a broad panel of in vivo xenograft models. These data highlight in vivo effects of schedule and order of drug administration in regimen efficacy and toxicity and have relevance to the design of human regimens incorporating TH-302.

TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules

PubMed Central

Liu, Qian; Sun, Jessica D.; Wang, Jingli; Ahluwalia, Dharmendra; Baker, Amanda F.; Cranmer, Lee D.; Ferraro, Damien; Wang, Yan; Duan, Jian-Xin; Ammons, W. Steve; Curd, John G.; Matteucci, Mark D.

2014-01-01

Purpose Subregional hypoxia is a common feature of tumors and is recognized as a limiting factor for the success of radiotherapy and chemotherapy. TH-302, a hypoxia-activated prodrug selectively targeting hypoxic regions of solid tumors, delivers a cytotoxic warhead to the tumor, while maintaining relatively low systemic toxicity. The antitumor activity, different dosing sequences, and dosing regimens of TH-302 in combination with commonly used conventional chemotherapeutics were investigated in human tumor xenograft models. Methods Seven chemotherapeutic drugs (docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide) were tested in combination with TH-302 in eleven human xenograft models, including non-small cell lung cancer (NSCLC), colon cancer, prostate cancer, fibrosarcoma, melanoma, and pancreatic cancer. Results The antitumor activity of docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide was increased when combined with TH-302 in nine out of eleven models tested. Administration of TH-302 2–8 h prior to the other chemotherapeutics yielded superior efficacy versus other sequences tested. Simultaneous administration of TH-302 and chemotherapeutics increased toxicity versus schedules with dosing separations. In a dosing optimization study, TH-302 administered daily at 50 mg/kg intraperitoneally for 5 days per week in the H460 NSCLC model showed the optimal response with minimal toxicity. Conclusions TH-302 enhances the activity of a wide range of conventional anti-neoplastic agents in a broad panel of in vivo xenograft models. These data highlight in vivo effects of schedule and order of drug administration in regimen efficacy and toxicity and have relevance to the design of human regimens incorporating TH-302. PMID:22382881

Synthesis and evaluation of the inhibitory activity of the four stereoisomers of the potent and selective human γ-glutamyl transpeptidase inhibitor GGsTop.

PubMed

Watanabe, Bunta; Tabuchi, Yukiko; Wada, Kei; Hiratake, Jun

2017-11-01

2-Amino-4-{[3-(carboxymethyl)phenoxy](methoxy)phosphoryl}butanoic acid (GGsTop) is a potent, highly selective, nontoxic, and irreversible inhibitor of γ-glutamyl transpeptidase (GGT). GGsTop has been widely used in academic and medicinal research, and also as an active ingredient (Nahlsgen) in commercial anti-aging cosmetics. GGsTop consists of four stereoisomers due to the presence of two stereogenic centers, i.e., the α-carbon atom of the glutamate mimic (l/d) and the phosphorus atom (R P /S P ). In this study, each stereoisomer of GGsTop was synthesized stereoselectively and their inhibitory activity against human GGT was evaluated. The l- and d-configurations of each stereoisomer were determined by a combination of a chiral pool synthesis and chiral HPLC analysis. The synthesis of the four stereoisomers of GGsTop used chiral synthetic precursors that were separated by chiral HPLC on a preparative scale. With respect to the configuration of the α-carbon atom of the glutamate mimic, the l-isomer (k on =174M -1 s -1 ) was ca. 8-fold more potent than the d-isomer (k on =21.5M -1 s -1 ). In contrast, the configuration of the phosphorus atom is critical for GGT inhibitory activity. Based on a molecular modeling approach, the absolute configuration of the phosphorus atom of the active GGsTop isomers was postulated to be S P . The S P -isomers inhibited human GGT (k on =21.5-174M -1 s -1 ), while the R P -isomers were inactive even at concentrations of 0.1mM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heparin use in a rat hemorrhagic shock model induces biologic activity in mesenteric lymph separate from shock.

PubMed

Qin, Yong; Prescott, Lauriston M; Deitch, Edwin A; Kaiser, Vicki L

2011-04-01

Experimental data have shown that mesenteric lymph from rats subjected to trauma-hemorrhagic shock (THS) but not trauma-sham shock induces neutrophil activation, cytotoxicity, decreased red blood cell (RBC) deformability, and bone marrow colony growth suppression. These data have led to the hypothesis that gut factors produced from THS enter the systemic circulation via the mesenteric lymphatics and contribute to the progression of multiple organ failure after THS. Ongoing studies designed to identify bioactive lymph agents implicated factors associated with the heparin use in the THS procedure. We investigated if heparin itself was responsible for reported toxicity to human umbilical vein endothelial cells (HUVECs). Human umbilical vein endothelial cell toxicity was not induced by lymph when alternate anticoagulants (citrate and EDTA) were used in THS. Human umbilical vein endothelial cell toxicity was induced by lymph after heparin but not saline or citrate injection into trauma-sham shock and naive animals and was dose dependent. Activities of both heparin-releasable lipases (lipoprotein and hepatic) were detected in the plasma and lymph from THS and naive animals receiving heparin but not citrate or saline. Lymph-induced HUVEC toxicity correlated with lymph lipase activities. Finally, incubation of HUVECs with purified lipoprotein lipase added to naive lymph-induced toxicity in vitro. These data show that heparin, not THS, is responsible for the reported lymph-mediated HUVEC toxicity through its release of lipases into the lymph. These findings can provide alternative explanations for several of the THS effects reported in the literature using heparin models, thus necessitating a review of previous work in this field.

Behavioral responses of three armadillo species (Mammalia: Xenarthra) to an environmental enrichment program in Villavicencio, Colombia.

PubMed

Cortés Duarte, Alexandra; Trujillo, Fernando; Superina, Mariella

2016-07-01

Enrichment is a powerful tool to improve the welfare of animals under human care. Stress-related health and behavioral problems, as well as reproductive failure, are frequent in armadillos (Xenarthra, Cingulata, Dasypodidae) under human care, which hinders the development of successful ex situ conservation programs. Nevertheless, scientific studies on the effect of enrichment programs on armadillos are virtually non-existent. The objective of this study was to assess the impact of an enrichment program on the behavior of armadillos under human care. The behavior of 12 individuals of three species (Dasypus novemcinctus, D. sabanicola, and Cabassous unicinctus) maintained at Finca El Turpial, Villavicencio, Colombia, was recorded using scan sampling during three daily time blocks of 2 hr each before (4 weeks) and after (4 weeks) implementing an enrichment program. Enrichment did not stimulate the armadillos to change or extend their activity period. In general, activity levels were low during the entire study, and virtually no activity was recorded in the morning in any species, neither without nor with enrichment. The latter did, however, improve welfare by reducing abnormal and increasing natural foraging behaviors. All species were attracted by artificial termite mounds. Dasypus spp. showed special interest in cardboard boxes with food, while Cabassous was mainly attracted to hollow plastic balls filled with food. Our results suggest that separate enrichment programs need to be developed for different armadillo species, and that they should be applied during the time of day at which they are most active. Zoo Biol. 35:304-312, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Proteomic profiling of human plasma exosomes identifies PPAR{gamma} as an exosome-associated protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Looze, Christopher; Yui, David; Leung, Lester

Exosomes are nanovesicles that are released from cells as a mechanism of cell-free intercellular communication. Only a limited number of proteins have been identified from the plasma exosome proteome. Here, we developed a multi-step fractionation scheme incorporating gel exclusion chromatography, rate zonal centrifugation through continuous sucrose gradients, and high-speed centrifugation to purify exosomes from human plasma. Exosome-associated proteins were separated by SDS-PAGE and 66 proteins were identified by LC-MS/MS, which included both cellular and extracellular proteins. Furthermore, we identified and characterized peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}), a nuclear receptor that regulates adipocyte differentiation and proliferation, as well as immune and inflammatorymore » cell functions, as a novel component of plasma-derived exosomes. Given the important role of exosomes as intercellular messengers, the discovery of PPAR{gamma} as a component of human plasma exosomes identifies a potential new pathway for the paracrine transfer of nuclear receptors.« less

Midcingulate Motor Map and Feedback Detection: Converging Data from Humans and Monkeys.

PubMed

Procyk, Emmanuel; Wilson, Charles R E; Stoll, Frederic M; Faraut, Maïlys C M; Petrides, Michael; Amiez, Céline

2016-02-01

The functional and anatomical organization of the cingulate cortex across primate species is the subject of considerable and often confusing debate. The functions attributed to the midcingulate cortex (MCC) embrace, among others, feedback processing, pain, salience, action-reward association, premotor functions, and conflict monitoring. This multiplicity of functional concepts suggests either unresolved separation of functional contributions or integration and convergence. We here provide evidence from recent experiments in humans and from a meta-analysis of monkey data that MCC feedback-related activity is generated in the rostral cingulate premotor area by specific body maps directly related to the modality of feedback. As such, we argue for an embodied mechanism for adaptation and exploration in MCC. We propose arguments and precise tools to resolve the origins of performance monitoring signals in the medial frontal cortex, and to progress on issues regarding homology between human and nonhuman primate cingulate cortex. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.